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710 Cards in this Set
- Front
- Back
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˛ˇLecture 1
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Introduction
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Define "microbe"
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microscopic living thing
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Define "pathogen"
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a microbe that can cause disease
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What is virulence?
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a measure of how pathogenic an organism is; how capable of causing disease
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What is a virulence factor?
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a molecule that gives a microbe its virulence (can be lipid, carbohydrate, protein)
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What is an avirulent organism?
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one that does not cause disease
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What types of infections do low virulence microbes generally cause?
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opportunistic infections in immuno-compromised hosts
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What does "normal flora" mean?
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bacteria on skin and mucosal surfaces
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What is a commensal relationship?
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when bacteria live on the host but don't cause harm (normal flora), in fact normal flora have a beneficial relationship with the host
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What is a nosocomial infection?
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one acquired in the hospital
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What defines "infection"?
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A step beyond colonization; an organism crosses anatomical barriers, crosses cell surface, or host develops an immune response to the organism
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What defines "colonization"?
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an organism establishes and multiplies on the body surface
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What is the difference between infection and disease?
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infection can be asymptomatic
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What are the common steps of microbial pathogenesis?
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colonization or attachment, invasion (common but not obligatory), evasion of host defenses, host damage (several mechanisms exist)
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Name some areas of the body that have little normal flora?
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stomach and small intestine
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Name some areas of the body that have no normal flora?
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lower respiratory tract, sterile fluids (CSF, blood, urine, bile) pleural and peritoneal spaces
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What are a few examples of when normal flora cause infections?
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perforate into abdomen and cause abdominal infection; obligated anaerobes break off of gingival crevae and are aspirated, cause lung abscesses
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What are Koch's postulates for micobial role in disease?
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1. Pathogenic organism should always be present, 2. it should be specific for the disease in questions, 3. it should be able to induce disease (hard to show)
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Why is the microbial surface important?
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it is critical for attachment, it is the first thing seen by the host, it evokes innate immunity, many surface molecules are virulence factors, and it is a target for adaptive immunity
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What is a serotype?
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a strain of microbe recognized by a particular serum
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What is a nucleoid?
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single circular double-stranded DNA chromosome of bacteria
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Why is a nucleoid not called a nucleus?
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it is not membrane bound
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What is important about prokaryotic ribosomes as compared to eukaryotic ribosomes?
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prokaryotes have 70s; eukaryotes have 80s
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What chemical motif is found in the membranes of eukaryotes but not prokaryotes?
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sterols
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What is a cell envelope?
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all the layers that encircle and retain the cytoplasmic contents-- includes the peptidoglycan and cytoplasmic membrane
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What is the murein layer?
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a rigid cell wall composed of peptidoglycan
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What is the structure of the peptidoglycan backbone?
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N-acetylglucosamine and N-acetylmuramic acid (≤(1!í4) linkage); tetrapeptide side chains composed of alternating D and L amino acids are attached at the N-acetylmuramic acids and parallel chains of PDG are crosslinked at these side chains by transpeptidase
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How does lysozyme affect the peptidoglycan backbone?
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it breaks ≤(1!í4) linkages
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How do ≤-lactam antibiotics affect the peptidoglycan backbone?
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they disrupt transpeptidase, which links parallel PDG chains
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What are the functions of the peptidoglycan wall?
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shape+rigidity, prevents lysis, acts as polar barrier to block entry of hydrophobic compounds
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What are the functions of the prokaryotic cytoplasmic membrane?
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osmotic barrier, active transport of nutrients via permeases, DNA attachment site for nucleoid and plasmids (allows for segregation during division), mediates iron uptake and protein export, site of electron transport chain, site of PDG synthesis
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What is a mesosome?
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an invagination of cytoplasmic membrane; thought to promote cell division and chromosomal separation. More common in gram+ bacteria
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Who has more mesosomes, gram- or gram+?
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gram+
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What is important to know about bacterial protein synthesis?
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transcription is coupled to translation, and polygenic mRNAs are produced
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What is the "capsule"?
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layer of acidic polysaccharides that surrounds some organisms; usually composed of 2-3 sugars characteristic of organism; main function is defense against phagocytosis
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What is the main function of a capsule in bacteria?
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protect against phagocytosis
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What is the Quellung reaction?
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used to type bacteria (esp. S. pneumoniae) by its capsule; mix microbe with Ab against a known capsule, if capsule swells the antibody is reactive and the microbe is typed
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What are flagella made of?
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single proteinaceous helical filament of the globular protein flagellin
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What are the two main types of flagella described in this course?
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polar (e.g. Pseudomonas) and peritrichous (e.g. Enterobacteriaceae)
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What is glycocalyx?
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an adhesive polymer film that contains polysaccharides; helps inhibit phagocytosis of the organism, can help organism stick to surfaces
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What are some common storage granules?
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poly-≤-hydroxybutyrate (storage form for lipids), glycogen or starch (storage form for sugar), polymetaphosphate AKA volutin (a storage form for phosphate)
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How can volutin be visualized?
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metachromatic stai-- turns red in the presence of methylene blue
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What is a spore?
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a cryptobiotic form of an organism, resistant to heat, desiccation and freezing; genera include Bacillus and Clostridium
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What does the cross-section of a spore look like?
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coat-layers of keratin-like proteins with many disulfide bonds; cortex-2 layers of PDG (inner for stability, outer for autolysis); germ cell membrane; core (contains high concentrations of dipicolinic acid and calcium as well as materials for resuming growth).
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Lecture 2
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Bacterial Structure and Classification
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What is lipoteichoic acid?
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polymers of ribitol or glycerol. Also a virulence factor for Gram+ bacteria and major antigen of both Strep and Staph
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What is beta hemolysis?
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complete RBC hemolysis-- plate becomes clear
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What is alpha hemolysis?
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does not lyse RBCs-- plate has green zones that surround the colonies
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How can one differentiate between strep A, B and C and Pneumococci?
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using an agglutination test with different specific antisera
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Which has catalase, Strep or Staph?
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staph
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What is the only coagulase positive Staph species?
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Staph aureus
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Name some microbes that have spores?
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Bacillus antrhracis, Clostridium bolulinum
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Name some organsims that have a positive oxidase test?
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Neisseria and Pseudomonas
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What are some unique features of Gram- bacteria?
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lipoprotein- bound to PDG layer, porins let hydrophilic molecules through, outer membrane proteins (Yersinia invasions), Lipopolysaccharide (LPS) triggers Ab production and can cause septic shock syndrome
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What are the major nonmotile bacteria?
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Enterobacteriacae (Gram-) e.g. Klebsiella or Shigella; Bacillus anthracis (Gram+ rod)
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What is an important diagnostic test for TB?
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acid fast stain
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What test of sputum is used to confirm TB and why?
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PCR of sputum-- microbe grows too slow
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What are some of the characteristic symptoms of a Nocardia infection?
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brain and pulmonary abscesses
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What is a drawback of using PCR to charactrize a microbe?
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it does not tell you resistance of the organism
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What is the difference in cell envelope between Gram- and Gram+ bacteria?
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Gram+ have PDG 100-800A thick and a plasma membrane; Gram- have outer membrane 60-180A thick, PDG 20-30A thick, and an inner plasma membrane
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What is an important molecule in the PDG of Gram+ bacteria that functions in anchoring and adhesion?
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lipoteichoic acid (LTA)
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Do Gram+ bacteria have sex pili?
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no
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Where can one find permeases in Gram+ bacteria?
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in the cytoplasmic membrane
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What is a permease?
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a membane-bound carrier involved in the active transport of nutrients
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What is an important protein found on the surface of Gram- bacteria?
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lipopolysaccharide or endotoxin, of which the Lipid A moiety is responsible ofr endotoxic manifestations
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What is Lipid A?
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a part of lipopolysaccharide (found on Gram- bacteria) consisting of a Lipid A moiety bound to a long oligosaccharide chain by a core. The oligosaccharide chain helps to exclude hydrophobic compounds, and the lipid A moiety is responsible for endotoxic manifestations
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What are some important proteins found in the outer membrane of Gram- bacteria?
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nutrient binding proteins (NBPs), porins, adhesinons/evasions, lipoprotein
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What do nutrient binding proteins do?
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translocate nutrients to the periplasmic space
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Which organisms have a periplasmic space, Gram+ or Gram-?
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Gram-
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What do porins do?
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located in the outer membrane, these protein trimers bind covalently to PDG and restrict the entry of compounds greater than 800 MW
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What do adhesions/evasions do?
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allow bacteria to adhere to host structures or evade the immune system, respectively
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What does lipoprotein do?
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Found in Gram- bacteria, it covalently anchors the outer membrane to the PDB at tetrapeptides; also loosely linked to LPS
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What is contained n the periplasmic space?
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PDG, enzymes, penicillin binding protein, etc.
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What is membrane derived oligosaccharide?
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MDO is a glucan polymer inserted into the periplasmic space; it regulates the osmolality of the peripslamic space and adjusts viscosity to avoid lysis
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Do Gram- bacteria have permeases?
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yes; in the cytoplasmic membrane
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What is teichoic acid?
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a molecule found in Gram+ bacteria, it assists in anchoring and contributes to antigen specificity; composed of glycerol or gibitol residues with phosphodiester links that is attached to muramic acid residues
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What are fimbrae (or pili)?
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composed of a filament of pilin, they are located on the surface of Gram- bacteria and allow them to interact with the external environment
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What is the structure of a pilus?
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helical-- undergoes addition at the base
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What do sex pili do?
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genetic exchange; there are only a few per cell
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What do common pili or fimbriae do?
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adhere to lectins on host cells; almost 100 per cell; almost all Gram- bacteria have them, and they're usually chromosomally encoded
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What organism uses pili for evasion?
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Neisseria gonorrhoeae (Opa or Protein II)
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Lecture 3
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Bacterial Physiology
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What organism is a common cause of gas gangrene?
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Clostridium perfringens
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What is the first phase of growth when bacteria are introduced into an environment?
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lag phase-- genes are turned on or off as part of genetic adaptation
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What is the second phase of growth when bacteria enter an environment?
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log phase-- bacteria grow exponentially unless something occurs to stop them
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What is the third phase of growth when bacteria are introducted to an environment?
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stationary phase-- varies with species but can be quite long or even nonexistent
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What is the fourth phase of growth when bacteria enter an environment?
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death phase-- numbers decrease
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What is an example of a fast-growing bacteria?
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Clostridium
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What is an example of a slow-growing bacteria?
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Mycobacterium tuberculosis
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Why is the stationary phase important?
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It modulates the mode of transmission for disease-- e.g. Salmonella can live for a weeks in stationary, but Neisseria gonorrhea does not
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What is an example of a bacteria with a long stationary phase?
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salmonella
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What is an example of a bacteria with a short stationary phase?
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Neisseria gonorrhea
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What are some important nutritional requirements for bacteria?
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organic carbon, sulfur, nitrogen and energy
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How are iron-binding proteins relevant to bacterial infection?
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lactoferrins, Hb, Mb bind iron, which is a critical factor for bacterial growth; if a host can lower the availability of iron to bacteria they can slow growth
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What are the two main energy processes used by bacteria?
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fermentation and respiration
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How does fermentation work?
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organic carbon compounds are degraded; the organism gets energy without change in its redox potential-- does not require O2
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How does respiration work?
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organic carbon compounds are degraded and electron transport is used to harness energy; O2 is usually a terminal electron acceptor
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What is the major toxic metabolite of respiration?
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superoxide anion
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What are the three classifications of bacteria with respect to their oxygen usage?
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obligate anaerobe, obligate aerobe, facultative
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What are some byproducts of Clostridium metabolism?
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(fermentation) glucose is converted to pyruvate and then to butyric acid and C02 gas
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Why are diabetics at high risk for infection?
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high levels of blood glucose give bacteria plenty of food!
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What is a siderophore?
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a small iron-chelating molecule used by many free-living bacteria to obtain iron from the external milieu
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What is an aerobactin?
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a siderophore used by invasive strains of E. coli to capture iron from the host
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What is an example of a bacteria that uses siderophores to gain iron?
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E. coli
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What are the three main ways bacteria can get iron from their environment?
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siderophores, "stealing" from tansferrin/lactoferrin, heme breakdown
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What is an example of a bacteria that uses direct iron uptake from transferrin/lactoferrin?
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Neisseria
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What is an example of a bacteria that uses heme breakdown to get iron?
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Bacteroides
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What are some examples of fermentation end products made by bacteria?
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lactic acid (Streptococcus), propionic acid (Propionibacterium), mixed acid (E. coli), butanediol (Klebsiella), butyric acid+CO2 (Clostridium), ethanol (usually yeasts)
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What is a useful metabolic test for diffentiating between enterobacteriaceae?
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formic hydrogenlyase--- E. coli can break formic acid into CO2 and H2 when the pH drops below 6; Shigella cannot
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How coud you tell the difference between E. coli and Shigella?
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formic acid test-- E. coli can break down formic acid; Shigella cannot
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What bacteria ferment pyruvate to lactic acid?
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Streptococcus
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What bacteria ferment pyruvate to butanediol?
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Klebsiella
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What bacteria ferment pyruvate to mixed acids?
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E. coli
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What are key enzymes determining whether or not bacteria are aerobes?
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SOD or catalase
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What is a classic obligate aerobic bacteria?
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Mycobacterium tuberculosis
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What is a classic facultative bacteria?
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E. coli
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What is the only facultative Pseudomonas species?
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Pseudomonas aeruginosa
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How can Pseudomonal aerugoinosa use an electron chain that doesn't involve oxygen as a terminal electron acceptor?
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it uses nitrate
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How can Bacteroides fragilis use an electron transport chain that doesn't involve oxygen as a terminal electron receptor?
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it uses fumarate
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Give an example of a facultative ogranism that only uses fermentation?
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Streptococcus
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Give an example of a facultative organism that ferments and respires
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E. coli
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Given an example of a facultative organism that respires only
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Pseudomonas aeuginosa
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Give an example of an obligate aerobe
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M. tuberculosis
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Give an example of an obligate anaerobe that ferments only?
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Clostridium
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Give an example of an obligate anaerobe that ferments and respires
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B. fragilis
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Notes 3
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Bacterial Classification
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What is the most fundamental test in diagnostic microbiology
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Gram stain
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What are the steps involved in the Gram stain?
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small amt of organsim, flood with crystal violet, rinse and flood with Gram's iodine, rinse and elute with acetone, rinse and counterstain with safranin, rinse and dry and visualize
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What structure on Gram+ bacteria causes them to stain the way they do?
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thick PDG cell wall inhibits decolorization
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What stain is used to visualize mycobacteria?
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Ziehl-Neelsen/ Acid fast stain
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What does the Ziehl-Neelson (acid fast) stain help visualize?
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Mycobacterium
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What type of stain helps visualize Nocardia?
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modified acid fast (using a gentler organic acid e.g. 1% sulfuric acid); Nocardia are acid fast +
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What is a good stain to differentiate between Nocardia and Actinomyces?
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modified acid fast stain (stains Nocardia)
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What does the catalase test detect
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if a colony contains catalaze (e.g. Staph)
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When is a good time to use the catalase test?
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to differentiate between Staphylococcus and Streptococcus
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What does catalase do?
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used (e.g. by Staphylococcus) to convert H202 to H20 + 02 (involves the use of heme)
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What does a positive catalase test look like?
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a bubbling bacterial colony
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What does the coagulase test do?
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tests whether bacteria coagulate plasma around them; put the bacteria into rabbit plasma and see if it forms a clot
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How does coagulase help bacteria?
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resists phagocytosis
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What test would help differentiate between Staphylococcus aureus and non-pathogenic staphylococci?
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coagulase test
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What does the optochin test do?
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looks for bacterial lysis in the presence of ethyl hydrocupreine (optochin) on a blood agar plate-- used to differentiate between Streptococcus species
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When is the optochin test used?
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to differentiate between alpha-hemolytic stroptococci
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What test would differentiate between Streptococcus pneumoniae and other alpha-hemolytic Gram+ cocci that are catalase negative?
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optochin test
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What is a P disk?
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a disk of optochin used to test if bacteria lyse in its presence (optochin test)
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What is the major human pathogen of the beta-hemolytic stroptococci?
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Streptococcus pyogenes
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What is the bacitracin test?
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looks for bacterial lysis in the presence of bacitracin; specific to Streptococcus pyogenes, which is sensitive to bacitracin
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What is the only beta-hemolytic streptococcus that is sensitive to bacitracin?
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Strep pyogenes
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What is an A disk?
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a disk of bacitracin added to an inoculated blood agar plate to test for resistance (bacitracin)
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What test would differentiate between Streptococcus pyogenes and other beta-hemolytic streptococci?
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bacitracin test (pyogenes is bacitracin-sensitive)
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What is the oxidase test?
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bacterial colonies are exposed to methyl phenylenediamine, which is oxidized to a blackish purple color by colonies with a cytochrome c oxidase
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What are some noteworthy oxidase positive organisms?
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Pseudomonas and Neisseria
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Are enterobacteriae oxidase negative or positive?
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negative
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Lecture 4
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Bacterial Genetics
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What is the serotype of an important pathogenic E. coli
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O157:H7
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What encodes O157 virulence?
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a plasma with virulence genes and a lysogenic phage encoding a Shiga-like toxin
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Define "prototroph"
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an organism with a wild-type complement of genes enabling it to grown with a simple requirement for nutrients
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Define "auxotroph"
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a mutant unable to synthesize a required small molecule; needs this to grow
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Define "fastidious organism"
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wild-type bacteria with complicated growth requirements
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Define "episome"
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a nonessential genetic element (exists as integrated DNA or free in cytoplasm)
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What is a bacteria that has linear plasmids?
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Borrelia
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Define "conjugative plasmid"
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capable of transmitting itself between bacteria
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Define "nonconjugative" or "mobilizable" plasmid
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needs help of a conjugative plasmid to transmit
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Define "broad host range" plasmid
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capable of replication in many unrelated hosts
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Define "narrow host range" plasmid
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capable of replication in only a single or closely related hosts
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What is a bacteriophage?
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a virus that infects bacteria
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What are the two main categories of bacteriophage infections?
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lytic and lysogenic
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What is the difference between a lytic and a lysogenic bacteriophage infection?
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lytic-- phage DNA enters host cell, subverts machinery, grows and lyses host cell to release progeny; lysogenic-- phage DNA enters host cell, integrates into DNA (and can be passed on to daughter cells), under proper conditions DNA is excised and phages are generated by subverting host machinery, host cell is lysed to release progeny
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What are insertion sequences (IS)?
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small (1000-2000 bp) DNA fragments capable of inserting themselves into DNA but not capable of autonomous replication
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What enzyme allows insertion sequences to enter and exit DNA?
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transposases
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What are transposons?
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sequences that act like insertion elements flanking other genes such as antibiotic resistance genes
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What are the two subtypes of transduction?
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generalized (bacterial DNA transfer) and specialized (phage DNA+bacterial transfer)
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What are some of the features of generalized transduction?
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bacterial DNA is injected, any gene can be transferred, occurs at low frequency, no viral DNA is transferred to host, bacteria must be closely related, DNA is incorporated through homologous recombination
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What are some of the features of specialized transduction?
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transfer is mediated by mutant phage, usually only a few specific genes are excised, bacteria must be closely related, higher frequency than generalized transduction
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What is the classic lysogenic bacteriophage that loves E. coli?
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Lambda
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What is the most common mechanism of gene transfer betwen bacteria?
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conjugation
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How does conjugation work?
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sex pili bind bacteria to each other, one transfers single-stranded plasmid into the other
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What is a (rare) secondary event of conjugation that involves the chromosome
|
occasionally plasmids integrate into the chromosome and can initiate chromosomal transfer into another bacteria through conjugation; usually only get a partial copy of the chromosome (and none of the plasmid)
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Describe the process of transformation
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free DNA released by dying bacteria is taken up by other bacterial cells and incorporated into the chromosome
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What are some medically important natural transformers?
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Gram-: Streptococcus pneumoniae; Gram+: Neisseria gonorrhoeae, haemophilus influenzae, Helicobacter pylori
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What is the most important virulence factor of S. pneumoniae?
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capsule
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What characteristic of bacterial growth is common in pathogenic bacteria that undergo transformation?
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they are often autolytic in the stationary phase
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What are sigma factors?
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give specificity for promoter regions for RNA polymerases; sigma factors can be used to activate a wide range of genes in response to specific environmental changes
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What are two important sigma factors to know?
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heat shock sigma factor (ubiquitous, may respond to fever); stress or stationary phase sigma factor (common, tied to induction of virulence genes)
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What are type III secretion systems?
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mechanism of Gram- bacteria to secrete specific proteins into host cells; induced in response to signals from host cells or the milieu; form a channel through the bacterial and host cell membranes so virulence proteins are delivered directly into the host cell
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What is a system critical to disease causation in many Gram- pathogens?
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Type III secretion system
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What is a two component regulator?
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mechanism used by bacteria to sense the environment and respond; one component located in outer membrane senses environment and phoshporylates a transcription factor leading to the production of virulence genes
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What are some examples of two component regulators?
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toxR protein senses when cholera toxin is in the small bowel, Salmonella phoPQ senses low Mg and turns on virulence genes
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What are some of the virulence factors incorporated by O157:H7
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pathogenicity island codes for type III secretion system and adherence factors, plasmid coding for adherence, hemolysin, and a protease that degrades Factor V; lambda-like phage encoding shiga toxin, implicated in vascular damage and renal failure
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Why is it difficult to define bacterial species based on genomics?
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they often have phages and phage remnants in their DNA that can be conserved across species
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Where do pathogenic bacteria carry virulence factors (and antibiotic resistance)?
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in plasmids
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What are the three mechanisms by which bacteria can acquire new DNA?
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conjugation, transduction and transformation
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Are pathogenicity islands the work of phages or plasmids?
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no-- they are virulence genes not associated with a known mechanism
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Lecture 5
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Staphylocci
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What are some major features of staphylococci?
|
Gram+ cocci grow in clusters; divide perpendicular to last plane of division, catalase positive, facultative, have electron transport chain, non-spore forming, nonmotile
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|
What are some of the defining features of S. aureus?
|
coagulase positive, thermostat nuclease positive, high salt tolerance, mannitol positive, ribitol in their Teichoic acid, often produces golden pigment from carotenoids, hemolysis is seen on blood agar after 24-36 hours
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What are the two main coagulase negative staphylococci?
|
S. saprophyticus and S. epidermidis
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What are some defining features of S. saprophyticus?
|
Novobiocin resistant, glycerol in Teichoic acid
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What are some defining features of S. epidermidis?
|
most common isolate of staphylococci, Novobiocin sensitive, glycerol in Teichoic acid, slime is virulence factor (exopolysaccharide biofilm)
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What is the first test you would do on Gram+ cocci?
|
catalase test--drop H2O2 and see if it bubbles (Streptococcus is negative; Staphylococcus is positive)
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What is the first test you would do on Gram+ catalase+ cocci?
|
coagulase test (S. aureus is coagulase positive, other Staph is not)
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What bacteria makes a slime as its virulence factor and is often found on catheters in hospitals?
|
S. emidermidis
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What does S. aureus disease usually look like?
|
localized, toxin-mediated disease; folliculitis/furuncles/carbuncles/abscesses/cellulitis/wound infection, often post-trauma or post-surgery infection e.g. osteomyelitis/endocarditis/lung abscesses/septic arthritis; also food poisoning, scalded skin syndrome, bullous impetigo, toxic shock syndrome
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What is toxic shock syndrome?
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bacteremia is bacteria in blood, septicemia is bacteremia + clinical symptoms (e.g. tachycardia, hypotension) implying systemic response to infection
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What is interesting about immune response to S. aureus?
|
no protective (memory) response is made
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What is protein A?
|
virulence factor of S. aureus linked covalently to PDG (some released) that binds IgG at Fc
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What are important virulence enzymes made by S. aureus?
|
clumping factor (cefA) allows microbe to adhere to fibrinogen, coagulase (coa) stimulates conversion of fibrinogen to fibrin by binding prothrombin; staphylokinase causes clot dissolution and activates conversion of plasminogen to plasmin; hyluronidase hydrolyzes hyaluronic acids in ECM; lipase helps bacteria to disseminate
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What host protein to S. aureus use to coat itself and prevent phagocytosis?
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fibrin (activates prothrombin in calcium-independent manner by binding coagulase)
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What are the major toxins released by S. aureus?
|
± hemolysin (mushroom-like structure forms pores in eukaryotic membranes), ≤ hemolysin (sphingomyelinase toxic for monocytes), panton-valentine leukocidin (lethal to PMNs, causes IL-8 release), exofoliative exotoxin (ET-A on chromosome and ET-B on plasmid, cleaves stratum granulosum causing scalded skin syndrome and bullous impetigo, antigenic), toxic shock syndrome toxin (TSST-1, agr-quorum sensing, causes toxic shock through absorption in monocytes and Ab production), enterotoxin (SE types A-E, heat stable, causes food poisoning, SE B is superantigen)
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What is the most potent S. aureus hemolysin?
|
alpha-hemolysin
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What S. aureus toxin causes mastitis?
|
≤ hemolysin
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What S. aureus toxin causes scalded skin syndrome or bullous impetigo?
|
exfoliative exotoxin
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What S. aureus toxin is controlled by agr-quorum sensing?
|
toxic shock syndrome toxin
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What S. aureus toxins are antigenic?
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toxic shock syndrome toxin, enterotoxin
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What S. aureus toxin is a superantigen?
|
enterotoxin B
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How does a superantigen work?
|
it binds MHC II of monocytes and macrophages at a non-peptide recognition site; recognized by TCR V≤ and causes proliferation or apoptosis of T cells
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What does agr do in S. aureus?
|
stationary phase gene regulator responds positively to H+ ions and negatively to carbohydrates; up-regulates toxins and down-regulates surface proteins
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How does quorum sensing activate agr?
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RAP secretion, phosphorylates TRAP through two component signaling, which stimulates agr to make RNAIII, which regulates transcription
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What are the main resistances of S. aureus?
|
penicillin, beta lactams, intrinsic (methicillin)
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How is S. aureus beta lactam resistant?
|
typically Ty plasmid, 3-4 types that can be distinguished by substrate and immunologically
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What causes intrinisc resistance in S. aureus?
|
plasmid-mediated mutation in transpeptidase (causing decreased affinity for all ≤-lactams); production of transpeptidase is induced by penicillin exposure, causes resitance to all second-generation penicillins
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What are the second-generation penicillins
|
e.g. Methicillin, made against S. aureus, stable when attacked by ≤-lactamases
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How does S. aureus cause scalded skin syndrome?
|
ET-A toxin targets desmoglian
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What are some examples of pattern recognition proteins involved in the innate immune system?
|
recognize: LPS of Gram- cell wall, PDG and lipotechoic acid, mannose, flagellin, pilin, dsRNA (viruses), CpG-rich DNA (bacteria), zymosan (fungi)
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How do TLRs signal intracellularly?
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adaptor molecule MyD88 triggers IRAK, TRAF6 and TAK1, which phosphorylates IkB (leading to degradation), NF-∫B moves to nucleus;
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What are the 4 main functions of complement in innate immunity?
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local vasodilation, chemotaxis, opsonization, destruction of pathogens through MAC
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What are the important complement factors to remember?
|
C3a- vasodilation/permeability, C3b- opsonization, C5a neutrophil chemoattractant, C5b-C9- MAC
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What is the critical molecule involved in neutrophil chemotaxis?
|
ATP
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What are some (non-oxygen dependent) microbicidal proteins?
|
cationic proteins (cathepsin G) damage membranes, lysozyme hydrolyzes cell wall, lactoferrin sequesters iron, proteases digest organisms, defensins and cathelicidins are pore-forming
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What is involved in oxygen-dependent killing in the phagolysosome?
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NADPH oxidase, SOD, others
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What is a genetic disease that leaves patients extremely susceptible to recurrent staph infections?
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chronic granulomatous disease
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What are adhesins?
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lectins that bind sugar or carbohydrates and assist in microbial adhesion (also bind adhesin receptor on host cells)
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What are some proteins bacteria use to adhere to host cells?
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adhesins, pili and fimbriae, afimbial adhesins (pedicle), intimin (cytoskeletal rearrangements), Hp90, filamentous hemagglutinin (Bordetella pertussis),
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What are some major ways that bacteria evade the immune system?
|
block acidification of phagolysosome (mycobacteria, legionella), block phagosome-lysosome fusion (salmonella, chlamydia), escape from phagosome to cytoplasm (Shigella, Rickettsia), inherent resistance to oxidants/AMPs (Salmonella, Staphylococcus)
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What does Cholera look like?
|
Gram- rod causes sudden watery diarrhea and vomiting, can result in severe dehydration; secretes cholera toxin
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How does Cholera toxin work?
|
AB5 hexamer binds to GM1 receptor; A subunit enters cell and ADP-ribosylates AC increasing cAMP production; increased phosphorylation causes anion secretion, intracellular water follows anions
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What does the cell wall of Gram+ bacteria contain?
|
interlocking matrix of teichoic and lipotechoid acids
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What makes Staph resistant to oxidative bursts?
|
catalase
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What protein helps make Staph drug resistant?
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PBP2
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Is the piment important in Staph virulence?
|
apparently
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Lecture7
|
Streptococcus
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|
What are some characteristics of Streptococci?
|
Gram+ cocci grow in pairs or chains, facultative, cell division occurs in a single plane, unable to synthesize heme (no electron transport, catalase negative), auxotrophic, alpha/beta/gamma hemolysis
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What is alpha hemolysis?
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RBCs are intact but hemoglobin is converted to biliverdin
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What is beta hemolysis?
|
RBCs are lysed by hemolysin
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What is gamma hemolysis?
|
no hemolysis
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What is the test you would perform on Gram+, catalase-, ±-hemolytic Strep?
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Optochin test-- Strep. pneumoniae is optochin-sensitive, the others are not
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What are some characteristics of Strep. pneumoniae?
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Gram+, lancet-shaped diplococci, autolytic, natural transformer, transmitted by person-to-person spread, capsule is most important virulence factor
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What organism is the most common cause of bacterial pneumonia?
|
Strep. pneumoniae
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What is the most common cause of meningitis?
|
Strep. pneumoniae
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What are some infections commonly caused by Strep. pneumoniae?
|
pneumonia, otitis media, sinusitis, bronchitis, bacteremia, meningitis
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How does the capsule help protect Strep. pneumoniae from immune attack?
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is keeps C3b away from the cell wall
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How do you make a vaccine against an oligosaccharide for children younger than 18 months old?
|
conjugate an oligosaccharide to a protein and use that
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What part of Strep. pneumoniae triggers inflammation?
|
release of teichoic acid and PDG during autolysis (not the capsule); teichoic acid stimulates PAF production and mimics its activity; PDG binds CD14 on macrophages and induces cytokine secretion
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What does pneumolysin do?
|
not entirely clear; forms pores when inserted into eukaryotic membranes, may interfere with clearance mechanisms in the lung
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What does neuraminidase do?
|
may unmask cell-surface binding receptors; its effect on RBC membrane may lead to hemolytic-uremic syndrome (HUS)
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What does hyaluronidase do?
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may facilitate tissue spread
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What do IgA1 proteases do?
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may prevent IgA-mediated immune clearance
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|
How do you treat Strep. pneumoniae?
|
used to be uniformly PCN sensitive; now you have to test
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|
What disease does S. mutans cause?
|
biofilms ("plaque") that lead to dental caries
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What disease does S. gordonii cause?
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endocarditis
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How are ≤-hemolytic Streptococci further characterized?
|
Lancefield antigen (group A-H and K-V)
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What is the most virulent ≤-hemolysing streptococcus?
|
S. pyogenes
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What are some characteristics of Streptococcus pyogenes?
|
most virulent ≤-hemolysing Strep, exclusively human pathogen, sensitive to bacitracin
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What test helps differentiate between ≤-hemolytic strep?
|
bacitracin test; S. pyogenes is bacitracin sensitive; others are not
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What are some infections caused by S. pyogenes?
|
strep throat, cervical lymphadenitis, peritonsillar abscesses, pneumonia, empyema, impetigo, cellulitis, erysipelas, necrotizing fasciitis, Rheumatic fever, Glomerulonephriis, Scarlet Fever, Streptococcal toxic shock syndrome
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What is the most important virulence factor for Strep. pyogenes?
|
M protein
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Serious Strep infection has as some predisposing factors...
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chickenpox, skin trauma
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What is a precursor to Rheumatic fever caused by S. pyogenes?
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pharyngitis
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What is M protein and how does it work?
|
coiled-coil ±-helical protein that confers virulence to Streptococcus pyogenes; extends from cell envelope as fimbriae, prevents phagocytosis by inhibiting C3b deposition, adheres to epithelial cells, binds fibrinogen and can then bind plasmminogen
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Why is an antibody to M protein not protective against future Strep. pyogenes?
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high degree of variability
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What are the major bound virulence factors for Streptococcus pyogenes?
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M protein, lipoteichoic acid, F protein, hyaluronic acid capsule, C5a protease, IgG and IgA binding proteins, group A carbohydrate
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What does lipoteichoid acid do in S. pyogenes?
|
attached to M protein, may facilitate binding of fibronectin
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What does F protein do in S. pyogenes?
|
allows binding to fibronectin; made under high O2/low CO2 conditions (when M protein is not made), may or may not bind respiratory epithelial cells
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What does hyaluronic acid in the capsule do for S. pyogenes?
|
inhibits phagocytosis (looks like human ground substance), may also mediate GAS adherence and tissue invasion
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What does C5a protease do for S. pyogenes?
|
cleaves C5a and inhibits neutrophil chemotaxis in vitro
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What does gropu A carbohydrate do?
|
can stimulate antibody production (but antibodies produced are not opsonic), unknown role in pathogenesis
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What are the major secreted virulence factors for Strep. pyogenes?
|
hyaluronidase, streptolysin O, streptolysin S, streptokinase, streptococcal pyrogenic exotoxins and related superantigens
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Why is hyaluronidase useful?
|
destroys hyaluronic acid; may be important in spread through tissue during cellulitis
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What does streptolysin O (SLO) do?
|
oxygen labile hemolysin causes beta hemolysis; only active in reduced form; works by forming transmembrane pores; antibodies against it are often used to diagnose GAS infection
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What does streptolysin S (SLS) do?
|
oxygen stable, made in presence of serum, causes beta hemolysis, structurally similar to other Gram+ bacteriocin, nonantigenic, one of most potent cytotoxins known, important factor in pathogenesis of invasive infections such as necrotizing fascitis
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What hemolysin causes ≤ hemolysis on BAP?
|
streptolysin S
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What does streptokinase do?
|
hydrolyzes fibrin and other host proteins, helping organism spread through tissues (when bound to bacterial cell surface, plasmin is not inhibited by alpha-macroglobulin), purified enzyme from Gropu G Strep is used to dissolve blood clots, antigenic
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|
What do streptococcal pyrogenic exotoxins do?
|
best recognized: SPE-A, SPE-C, SPE-F; superantigens associated with scarlet fever and toxic shock
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What Strep virulence factor is associated with scarlet fever and toxic shock syndrome?
|
SPE-A
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What does SPE-B do?
|
cysteine protease that is chromosomally encoded, cleaves precursor IL-1B to its active form; can degrade fibronectin and vitronectin
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|
What is the treatment of choice for S. pyogenes?
|
penicillin, also clindamycin and erythromycin; clindamycin cuts down protein synthesis/toxin production; finally, IV Ig as adjunctive therapy
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What are some characteristics of the Group B strep?
|
AKA S. agalactiae, split up based on surface polysaccharide capsular Ags, don't produce large zones of hemolysis (do present orange pigment), normal vaginal/intestinal flora in 20-30% of adults, can gain stepwise access to bloodstream
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Who is more susceptible to group B strep?
|
children
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|
What is a common route of infection by GBS in babies?
|
organism colonizes vagina, ascends and infects amniotic fluid through placental membranes, fetus aspirates organism in amniotic fluid; also, through the birth canal.
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|
What is a common route of infection by GBS in newborns?
|
invasion of alveolar and pulmonary enothelial cells
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|
What is the leading cause of pneumonia, septicemia, and meningitis in newborns?
|
group B strep (GBS)
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|
What is a simple preventive measure that can protect against transmission of GBS to the newborn from the mother?
|
test vagina for GBS and treat with antibiotics if needed
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|
What are common GBS infections in the first days of life?
|
pneumonia and septicemia; risk factors include low-weight preemies and premature membrane rupture; presents like respiratory distress syndrome +fever, widespread injury to lung tissue with alveolar hemorrhage and protein exudate; all capsule types are implicated
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|
What are common late onset GBS infections (5-30 day olds)
|
bacteremia and meningitis
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|
What is the most common strain of late onset bacteremia/meningitis?
|
capsule type III; GBS strains have ability to cross BBB through attachment and invasion of brain capillary cells
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|
What organism causes bovine mastitis?
|
GBS
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|
What is a test that helps diagnose GBS?
|
CAMP test
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|
How does the CAMP test work?
|
Strep. agalactiae produces toxin that gives strong hemolysis in presence of S. aureus beta-hemolysin; CAMP test is a perpendicular (not touching) streak of S. agalactiae w/ S. aureus and look for an arrowhead of ≤-hemolysis
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What are some major virulence factors for S. agalactiae?
|
polysaccharide capsule (sialic acid), ≤-hemolysin, C5a peptidase
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How does the GBS capsule block immune attack?
|
contains sialic acid displayed in terminal linkage similar to those on human cells; inhibits binding of C3 to cell surface; (also mimics host protein)
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|
What is an important mechanism of immunity against GBS in fetuses?
|
anticapsular IgG transmitted transplacentally
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|
How does ≤-hemolysin help GBS?
|
it is cytotoxic to pulmonary epithelial and endothelial cells; contributes to pulmonary injury in pneumonia, also provokes inflammatory response/cytokine release/NO production
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What endogenous factor blocks GBS ≤-hemolysin?
|
surfactant
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|
Why might premature infants be susceptible to GBS?
|
surfactant blocks activity of GBS ≤-hemolysin
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|
How is GBS treated?
|
penicillin, ampicillin, cephalosporin
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|
What are common diseases caused by ≤-hemolytic group C Streptococcus?
|
uncommon infective agent, but causes syndromes similar to group A including cellulitis and lymphangitis
|
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|
What are Group D ≤-hemolytic Streptococci?
|
genus Enterococcus
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|
What are some common enterococci?
|
E. faecalis and E. faecium
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|
When do enterococci cause disease?
|
outside of their normal places (e.g. UTI, endocarditis, abscesses)
|
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|
What medium helps differentiate between Enterococcus from S. bovis?
|
esculin+ (metabolize to black pigment), 40% bile, and high salt; S. bovis can do bile and esculin, but not high salt
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|
What is a paradoxical treatment for endocarditis due to Enteroccoccus?
|
a penicillin + an aminoglycoside (enterococci are penicillin tolerant and should be intrinsically resistant to aminoglycoside, but the two are synergistic and it works)
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|
Are Enterococci hemolytic?
|
not always, but hemolysis is related to virulence
|
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|
Where is hemolysin encoded in Enterococci?
|
plasmid
|
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|
What antibiotics do Enterococci resist?
|
penicillins
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|
What is the treatment for Enterococci?
|
vancomycin in combnation with an aminoglycoside or penicillin+aminoglycoside
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Why is vancomycin resistance in Enterococci scary?
|
some enterococci have recently developed vancomycin resistance, everybody's scared that it will get transferred to other species like methicillin resistant S. aureus. Then they would be killers
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|
What is a common secondary problem caused by infection with group A strep?
|
glomerulonephritis due to Ag-Ab complexes
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|
What protein interaction helps Group A Strep invade?
|
binding to CD44 (hyaluronic-acid-binding protein); other adhesions are to fibronectin, fibrinogen and laminin
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|
What is sfb-1 (in GAS)?
|
fibronectin binding protein that helps GAS attach,
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Where is SPE-A encoded?
|
plasmid
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|
What antigen is associated with scarlet fever?
|
GAS exotoxin SPE-A
|
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Do streptococci have an electron transport chain?
|
no
|
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|
What is the metabolic end-product of streptococcal metabolism?
|
lactic acid
|
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|
What bacteria helped elucidate DNA as the genetic material?
|
S. pneumoniae
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|
Lecture 8
|
Family Enterobacteriaceae
|
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|
What is the structure of Enterobacteriaceae?
|
Gram- rods
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|
What are some characteristics shared by all Enterobacteriaceae?
|
Gram- rods, short with rounded edges (typically 4-5 microns), don't produce spores, have peritrichous flagella, most have pili or fibriae, oxidase negative, facultative organisms, ferment glucose to pyruvate, reduce nitrate to nitrite
|
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|
Which Enterobacteriaceae are nonmotile?
|
Klebsiella and Shigella
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|
Do Enterobacteriaceae have electron transport chains?
|
yes-- but they are cytochrome c negative
|
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|
How are Enterobactericaeae grossly characterized?
|
antigenically: K, H and O antigens
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|
What is K (Vi) antigen?
|
the acidic polysaccharide capsule of Enterobacteriaceae
|
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|
What is the function of the Enterobacteriaceae capsule?
|
evasion (antiphagocytic), adhesion (to GI or GU epithelia)
|
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|
Why is E. coli capsule type K1 special?
|
it is associated with adherence to other lectins of the GU epithelium in nephritogenic strains; also associated with neonatal meningitis (since it is antiphagocytic, anticomplementary, and resembles scialic acid)
|
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|
What is H antigen?
|
flagella-- Klebsiella and Shigella lack H antigen
|
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|
What is O (or Somatic) antigen?
|
polysaccharide side chain of endotoxin or LPS; also certain O antigens promote GU adhesion
|
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|
What is the toxic component of LPS?
|
Lipid A; it is exposed when cells are lysed
|
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|
What are the main types of Enterobacteriaceae pili?
|
1-4; Type 1 are mannose sensitive and important for GI colonization; Type 2 are mannose resistant and are important virulence factors that help organisms cause disease outside their normal niche
|
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|
What are the main types of Enterobacteriaceae fibrae?
|
P fimbrae: bind to neutral glycolipids of the bloboside series (found on human P blood group); X adhesins: bind to different globosides; BFP or bundle-forming pili: polar, participate in attachment of certain pathogenic E. coli to host cells
|
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|
What type 2 pili are associated with nephritogenic E. coli?
|
P fimbriae and X adhesins
|
|
|
What are the main enterobacteriaceae important to our studies?
|
Escherichia, Shigella, Proteus, Salmonella, Klebsiella, Yersinia
|
|
|
What Enterobacteriaceae are unable to ferment lactose?
|
Shigella, Salmonella, Yersinia
|
|
|
What is the general appearance of Enterobacteriaceae cultures?
|
dome-shaped, gray, smooth
|
|
|
What is the selectivity of EMB agar?
|
eosin inhibits Gram+ organisms, only sugar is lactose (and pH sensor will change if colony is fermenting), peptone is energy source if organism cannot ferment lactose (colorless colonies)
|
|
|
What is the selectivity of MacConkey agar?
|
high bile content inhibits Gram+ organisms, lactose fermenters produce acid and pH will cause colony to be colored; if not peptone will be used for energy and no color change seen
|
|
|
What metabolic process is common to the pathogenic Enterobacteriaceae?
|
unable to ferment lactose
|
|
|
What are the two possible metabolic pathways for breakdown of pyruvate in Enterobacteriaceae?
|
conversion to mixed acid (formic acid, acetic acid, lactic acid, succinic acid, more), or conversion to 2,3-butanediol (+ethanol and enough acid to change the color on a lactose fermentation plate)
|
|
|
What does the Voges-Proskauer test do?
|
detects the use of the butanediol pathway; detects a color change caused by acetoin (an intermediate); formic acid from this pathway can be converted into CO2 and H2 if the bacterium has formic dehydrogenase
|
|
|
Why doe E. coli and K. pneumoniae have different colors on a lactose fermentation plate?
|
E. coli uses the mixed acid pathway, it makes so much acid that it can turn green; K. pneumoniae uses the butanediol pathway and makes just enough acid to turn blue
|
|
|
What does the lactose fermentation test separate?
|
lactose fermenters (E. coli, Citrobacter, Klebsiella, Enterobacter) from the non-lactose fermenters (Shigella, Salmonella, Yersinia, Proteus, Serratia)
|
|
|
What are the primary pathogens among Enterobacteriaceae?
|
Shigella, Salmonella, Yersinia, (can be E. coli, Klebsiella pneumoniae)
|
|
|
What are the opportunistic pathogens among Enterobacteriaceae?
|
Proteus, (can be E. coli and Klebsiella pneumoniae)
|
|
|
What is an adhesin?
|
any of a group of macromolecules on the exterior cell envelope of bacteria that is involved in adherence
|
|
|
What are type 1 pili good for?
|
expressed in stationary phase, allow enteric bacteria to colonize the gut; able to be regulated; mediate phagocytosis by PMNs;
|
|
|
What are type 2 pili good for?
|
important virulence factors that help organism cause disease outside of normal niche
|
|
|
Name some famous adhesins
|
P pili (E. coli) allow binding to glycolipid on urethral and renal epithelial cells; F protein of S. pyogenes allows binding to amino terminus of fibronectin; filamentous hemagglutinin (B. pertussis) mediates binding to host cells
|
|
|
What do invasins do?
|
proteins that act locally to damage or invade a host cell and/or facilitate growth and spread of a pathogen
|
|
|
What does invasin do in Yersinia enterocolitica
|
binds cellular ≤-1 integrins with high affinity, causes rearrangement of cytoskeleton which results in uptake of organism
|
|
|
What is special about the capsule of S. typhi?
|
covers C3 binding sites on its LPS
|
|
|
What is special about the capsule of K1 E. coli?
|
heavily sialylated-- prevents activation of alternative complement pathway by the binding of factor H to the surface
|
|
|
What are important E. coli toxins?
|
LT toxin (activates AC), ST toxin (binds guanylate cyclase), Shiga toxin (inhibits host protein synthesis), RTX or hemolysin (pore-forming protein)
|
|
|
Where is LT toxin found and what does it do?
|
found in enterotoxigenic E. coli, plasmid encoded, binds and ribosylates alpha subunit of Gs; continually stimulates AC causing secretion of Cl-, Na+ and H2O
|
|
|
Where is ST toxin found and what does it do??
|
found in enterotoxigenic E. coli, plasmid encoded, binds guanylate cyclase on brush border, elevates intracellular cGMP causing Cl- secretion
|
|
|
Where is Shiga toxin found and what does it do?
|
found in Shigella dysenteriae (chromosomally encoded) and enterohemorrhagic E. coli (phage encoded), two component cytotoxin that cleaves an adenosine residue in the 60s subunit of rRNA, inhibiting host protein synthesis
|
|
|
Where is RTX (hemolysin) found and what does it do?
|
found in some invasive E. coli, pore-forming protein secreted by ABC transporter; lyses RBCs but probably more important in killing phagocytic cells; E. coli causing meningitis usually make RTX
|
|
|
What is interesting about the E. coli iron transporter?
|
in addition to iron, it is a receptor for bacteriophages, a binding cyte for colicin and for the antibiotic albomycin
|
|
|
What is the substrate for the antibiotic albomycin?
|
the iron transporter of E. coli
|
|
|
What is a pathogenicity island?
|
a contiguous set of chromosomal virulence genes that has been transported from one bacterial species to another
|
|
|
What bacteria binds CFTR?
|
Salmonella typhi, cause of typhoid fever, binds to CFTR
|
|
|
Why might cystic fibrosis be protective?
|
the "F508 mutation prevents S. tyhpi binding to CFTR
|
|
|
How does Salmonella use a type III secretion system to invade host cells?
|
under anaerobic conditions, Salmonella uses type III secretion system to inject a tyrosine kinase that phosphorylates CDC42 causing actin polymerization, leads to ruffles in cell membrane where bacteria cluster and are endocytosed into vacuoles; a tyrosine phosphatase is also secreted which dephosporylates CDC42 allowing the cell membrane to return to normal shape; another type III secretion system is activated inside phagosomes and a small protein is secreted into cytoplasm that interferes with lysosomal trafficking in cells
|
|
|
How does Yersinia use a type III secretion system?
|
Yops antigens are induced by contact with host cells and injected into them via type III secretion; YopH is a tyrosine phosphatase that dephosphorylates all tyrosine related hos protein including focal adhesion kinase which is involved in integrin signaling; yertain Yops antigens also prevent actin polymerization and therefore prevent phagocytosis of the organism
|
|
|
How does Shigella use a type III secretion system?
|
to invade cells
|
|
|
What is a critical feature of bacteria capable of being a systemic pathogen and how do they do it?
|
need to evade complement-mediated lysis; accomplished by long polysaccharid chains in the LPS; C3 binds terminal sugars of these long O side chains and assembly of the MAC is far away; some capsules may also mediate MAC resistance
|
|
|
Do Enterobacteriaceae have a positive or negative oxidase test?
|
negative
|
|
|
What do Gram stained Enterobacteriaceae look like?
|
clothespins
|
|
|
What are the 4 groups of Enterobacteriaceae?
|
Group I: makes acid and turns methyl red test positive; Group II: makes alcohols, does not make acid and thus has negative methyl red test; Group III: deaminates phenylalanine; Group IV: recently added, makes mixed acid and has lower optimal temp
|
|
|
What does Serratia look like?
|
red-pigmented shown to cause disease in immunocompromised individuals
|
|
|
What does Proteus mirabilis commonly cause and why can it be hard to eradicate?
|
causes UTIs; has potent urease that generates ammonia-- ammonia can make alkaline environment and cause stones, and bacteria can inhabit stones
|
|
|
What causes hemorrhagic colitis in O157:H7?
|
plasmid-encoded protase that degrades factor V
|
|
|
What causes hemolytic uremic syndrome?
|
shiga toxin
|
|
|
How does Salmonella bacteremia present?
|
as osteomyelitis, meningitis or aortitis
|
|
|
What organisms cause enteric disease?
|
S. typhi and S. paratyphi
|
|
|
What is the pathology of S. typhi infection?
|
Vi capsule covers C3 binding site on LPS, S. typhi crosses epithelial cells and invades submucosa, M cells pick up bacteria and transport it to liver, spleen, bone marrow; causes heptosplenomegaly, mysenteriy lymphadenopathy and inflammation of Peyer's patches/spleen with severe inflammation and possible intestinal rupture; (organism can also reach gall bladder and form gall stones)
|
|
|
What is important about the infectious dose of Shigella?
|
very low (10-200 organisms)
|
|
|
What are the four transmission vectors for Shigella?
|
fingers, food, flies, feces
|
|
|
Where do we get Yersinia?
|
animal hosts
|
|
|
What organism causes bubonic plague?
|
Y. pestis, causes buboes, fever and conjunctivitis
|
|
|
What organism causes Pneumonic plague?
|
Y. pestis, mainly from transfer via respiratory route; Sx include HA, weakness, cough, pneumonia and rapid cyanosis
|
|
|
What organism found in raw milk and animals causes invasive enterocolitis, mesenteric adenitis, and reactive arthritis, is capable of growing in a cold environment and associated with infections after blood transfusions?
|
Y. enterocolitica
|
|
|
First UTI in a female is usually what organism?
|
E. coli
|
|
|
What organism commonly causes UTIs?
|
Proteus
|
|
|
If a patient has infection associated with instrumentation and also has stones, what is a good candidate?
|
Proteus
|
|
|
Who is at risk for a Klebsiella pneumonia? What might it look like?
|
alcoholics and hospitalized patients, sputum looks like red currant jelly
|
|
|
What is a common soil pathogen?
|
Proteus
|
|
|
Lecture 9
|
Pseudomonas
|
|
|
What are some general characteristics of Pseudomonas?
|
Gram- rods, polar flagella, oxidase positive, respire only, nutritionally versatile
|
|
|
What sets Burkholderia mallei apart from Pseudomonas?
|
it is non-motile
|
|
|
What sets Stenotrophomonas maltophilia apart from Pseudomonas?
|
it is oxidase negative
|
|
|
What is the main metabolic pathway for sugars in Pseudomonas?
|
via 2-keto-deoxygluconate (AKA Entner Douderoff) pathway
|
|
|
Pseudomonas are generally what metabolic category?
|
obligate aerobes relying on electron transport for ATP
|
|
|
What is unique about P. aeruginosa?
|
major pathogen of Pseudomonas, can survive anaerobic environments using nitrate as erminal electron acceptor
|
|
|
Where is Pseudomonas aeruginosa found?
|
nearly everywhere; frequently contaminates respiratory equipment, humidifiers, sinks, more
|
|
|
What are the metabolic needs of Pseudomonas?
|
very simple-- can grow even in antiseptic, saline and soap solutions
|
|
|
What is an important feature of the metabolic by-products of Pseudomonas?
|
they don't turn the medium acid
|
|
|
What does Pseudomonas look like on agar?
|
BAP: three colony types; agar: extracellular pigments that diffuse into agar
|
|
|
What are important extracellular proteins of Pseudomonas
|
fimbriae used for attachment/colonization, alginate (exopolysaccharide capsule) allows adhesion of bacteria to each other and also antiphagocytic; pyochelin is siderophore
|
|
|
What is pyochelin?
|
siderophore of P. aeruginosa
|
|
|
What does alginate do?
|
exopolysaccharide capsule of P. aeruginosa (composed of D-mannuronic and L-gluronic acid), inhibits ciliary clearance, allows bacteria to adhere to one another, antiphagocytic, causes a lot of Ab production in CF patients (but acts as a blocking Ab)
|
|
|
What is important about the constitutively produced capsule of Pseudomonas?
|
associated with cystic fibrosis patients
|
|
|
Why is antibody against Pseudomonas capsule not useful?
|
it's a blocking antibody
|
|
|
What is Pseudomonas endotoxin like?
|
similar to Enterobacteriaceae, but O side chains are different-- not attached to the core, and also has Ca pyrophosphate link that helps make outer membrane very impenetrable
|
|
|
What is important about the Pseudomonas outer membrane?
|
very impenetrable-- due to Ca-pyrophosphate links of endotoxin
|
|
|
How are pigments important to Pseudomonas?
|
pigments (fluorescein AKA pyoverdin, pyocyanin is blue-green, pyorubin is rust brown, ±-oxyphenazine is colorless breakdown product of pyocyanin) are toxic to WBCs (esp. pyocyanin to neutrophils), increased production on minimal media and in low iron conditions, they have antibiotic properties
|
|
|
What organsim makes fluorescein?
|
Pseudomonas!
|
|
|
What test is useful for detecting Pseudomonas infection in burn patients?
|
fluorescein
|
|
|
What are some good exotoxins made by Pseudomonas?
|
Pyocins (bacteriocins), exotoxin A (inhibits protein synthesis), exotoxin S (modifies GTP-binding proteins, stimulates inflammatory cytokines)
|
|
|
What does Exotoxin A do?
|
induced by iron limitation, binds to receptors and enters host cytoplasm and ADP-ribosylates EF2, leading to inhibition of protein synthesis; convergent evolution with diptheria toxin, destroys cells during corneal infections
|
|
|
What do diptheria toxin and exotoxin A have in common?
|
both inhibit protein synthesis through ADP-ribosylation of EF2 (convergent evolution!)
|
|
|
What is one of the nastiest enzymes produced by Psuedomonas?
|
elastase-- accounts for "vascular tropism" of organism, and causes ecthyma gangrenosum; destroys blood vessel linings and implicated in hemorrhagic and necrotic lesions of lung and skin
|
|
|
What are some of the enzymes and proteases produced by Pseudomonas?
|
gelatinase, collagenase, lecithinase, neutral and alkaline protease, elastase (nasty!), phospholipase C, cytotoxin
|
|
|
What does Pseudomonas' phospholipase C do?
|
TTSS secreted, requires host factors to be active, cytotoxic
|
|
|
What are the main regulators of Pseudomonas activity?
|
Las R-- coordinate regulator of protease transcription, elastase and exotoxin A; Las I is autoinducer coordinating action of LasR
|
|
|
What causes quorum sensing in Pseudomonas?
|
Las I is autoinducer coordinating action of LasR; at high enough concentrations it affects LasR's actions
|
|
|
Does Pseudomonas have low or high antibiotic resistance?
|
high
|
|
|
What are some of the mechanisms of resistance of Pseudomonas to antibiotics?
|
≤-lactamases, aminoglycoside inactivating enzymes, chloramphenicol acetylating enzymes, tetracycline expulsion, altered drug targets (e.g. penicillin binding proteins and gyrase)
|
|
|
Is P. aeruginosa common in healthy individuals?
|
no
|
|
|
What are some of the good host defenses against P. aeruginosa?
|
normal body surfaces, intact normal flora, complement-mediated lysis, neutrophils
|
|
|
Why are P. aeruginosa infections common in hospitals?
|
patients on one antibiotic have decreased normal flora, which are protective against P. aeruginosa, but P. aerguniosa is resistant to the antibiotic in use
|
|
|
What diseases are common in immunocompromised patients infected with P. aeruginosa?
|
neutropenics: bacteremia and pneumonia; UTIs; CF patients: respiratory tract infection, IV drug users: endocarditis; burn patients: osteochondritis/osteomyelitis; ecthyma gangrenosum; corneal infections, hot tub folliculitis and external otitis
|
|
|
Why are CF patients susceptible to respiratory tract infections by P. aeruginosa?
|
blocking Abs made against the alginate, ciliary clearance is inhibited, CF cells lack the receptor and do not engulf Pseudomonas
|
|
|
What is the most common pathogen causing osteochondritis after a puncture wound to the foot?
|
P. aeruginosa
|
|
|
What is the most common cause of ecthyma gangrenosum?
|
P. aeruginosa
|
|
|
What is the pathology of ecthyma granulosum?
|
necrotic skin lesion; serum resistant and complement resistant P. aeruginosa invades tissue-- a little spot of local necrosis is first seen, then infection disseminates; invasion of blood vessels (vascular tropism) allows elastase to destroy vessel causing cloting, obstruction, or necrosis
|
|
|
What is a pathogen that causes hot tub folliculitis?
|
P. aeruginosa
|
|
|
What is Burkholderia mallei
|
formerly Pseudomonas mallei; non-motile Pseudomonad, causes glanders (horse disease characterized by pneumonia and necrosis of mucous membranes, skin and lymphatics) can be transferred from horses to humans
|
|
|
What is Burkholdeeria pseudomallei
|
formerly Pseudomonas pseudomallei; found in tropical soil of SE Asia, infection can be dormant for years, causes melioidosis (chronic lung disease often initially misdiagnosed as TB) and bacteremia; has multitrichous polar flagella
|
|
|
What pathogen causes melioidosis?
|
B. pseudomallei
|
|
|
What is Burkholderia cepacia?
|
formerly Pseudomonas cepacia; important opportunistic pathogen in CF and CGD patients but otherwise rarely causes disease; very resistant to antibiotics (usually susceptible to piperacillin and third generation cephalosporins), has multitrichous polar flagella
|
|
|
What is Stenotrophomonas maltophilia?
|
formerly Pseudomonas maltophilia, third most common Gram- pathogen, common nosocomial opportunistic pathogen but has low virulence, very resistant to antibiotics including carbapenems (TMP/SMX is drug of choice),
|
|
|
What Pseudomonas species can infect blood transfusions and medication stores, and grows at 4∞
|
P. fluorescens
|
|
|
What is the common environmental habitat of Pseudomonas aeruginosa?
|
plant pathogen (also nosocomial)
|
|
|
What are the main lines of defense against Pseudomonas invastion?
|
neutrophils, then intact epithelium, then normal lung structure
|
|
|
What two groups of patients tend to get Pseudomonas?
|
neutropenic patients, IV drug users, CF patients
|
|
|
What are some Pseudomonas-like organisms?
|
Burkholderia (nonmotile), Stenotrophomas (oxidase-), Acinetobacter (oxidase-, nonmotile)
|
|
|
Lecture 9
|
Acinetobacter
|
|
|
What is an important nosocomial pathogen not Pseudomonas or Stenotrophomonas
|
Acinetobacter
|
|
|
What is the only Gram- that is part of normal skin flora?
|
Acinetobacter
|
|
|
What is the most disease-causing Acinetobacter?
|
A. baumannii
|
|
|
What are some characteristics of Acinetobacter?
|
Gram-, rod-shaped during log phase but coccobacillary during stationary phase, nutritionally versatile, oxidase negative, respire only, unable to reduce nitrate
|
|
|
What helps differentiate Acinetobacter from Neisseria or Moraxella?
|
Acinetobacter are oxidase negative
|
|
|
What helps differentiate Acinetobacter from Enterobacteriaceae?
|
they respire only, and they cannot reduce nitrate
|
|
|
What are some of the features of Acinetobacter colonies?
|
nonpigmented and may be mucoid (due to capsule)
|
|
|
Why can it be hard to identify Acinetobacter using Gram stain?
|
they have a tendency to retain crystal violet and can therefore seem Gram+; also they are coccobaccili in stationary phase
|
|
|
What are the virulence factors associated with Acinetobacter?
|
capsule (inhibits phagocytosis, may predispose people with selective complement deficiencies to infection), LPS (not sure), bacteriocins
|
|
|
What is the antibiotic resistance of Acinetobacter?
|
high resistance to antimicrobials, mechanisms include ≤-lactamases, alteration of penicillin-binding proteins and gyrase, loss of porins, efflux pump
|
|
|
What bacteria is causing antibiotic-resistant wound infections in Iraq?
|
Acinetobacter
|
|
|
How is Acinetobacter acquiring drug resistance?
|
acquisition and transfer of resistance via plasmids and transposons
|
|
|
What are risk factors for Acinetobacter infection?
|
severe illness, immunocompromised state of host, extended stays in ICU, previous administration of third generation cephalosporins, procedures such as intubation, ventilator use, indwelling catheter and neurosurgery
|
|
|
What are some common diseases caused by Acinetobacter?
|
pneumonia, bacteremia, meningitis, other infections (cellulitis with indwelling venous catheter, cystitis/pylonephritis with indwelling urinary catheter, traumatic wound/burn/incision infection, common Iraqi war infection)
|
|
|
How should Acinetobacter be treated?
|
combination therapy, infection control procedures
|
|
|
Lecture 10
|
Campylobacter and Helicobacter
|
|
|
What are some important characteristics of Campylobacter species?
|
Gram- rods that may have appearance of gull wings, oxidase positive, polar flagella (characteristic darting motility), fastidious and slow growing, require special conditions: microanaerobic, capnophilic, ferment peptones but not carbohydrates, 42∞ C is optimal
|
|
|
Where are Campylobacter species often found?
|
GI flora of many wild and domestic animals, esp pigs and birds; chicken is most likely meat to spread; no person to person spread
|
|
|
Why is person to person spread difficult in Campylobacter?
|
there is no long-term carrier state in humans
|
|
|
Who gets Campylobacter?
|
children in developing countries, adults in developed countries, children and elderly die
|
|
|
What is an important natural sensitivity of Campylobacter?
|
gastric acid
|
|
|
What are the culture demands of Campylobacter?
|
microaerophilic (want low oxygen 5-10%), capnophilic (want high CO2 4-8%), can ferment peptones but not carbohydrates, thermophilic (C. jejuni and C. coli like 42∞C)
|
|
|
What pathogens are the leading cause of acude diarrhea worldwide?
|
Campylobacter jejuni and Campylobacter coli; cause watery or inflammatory diarrhea of jejunum, ileum and colon
|
|
|
What are the symptoms of Campylobacter infection?
|
fever, diarrhea, abdominal cramping; diarrhea can be diffuse and blood is found in stool by second or third day, tends to last 4-5 days
|
|
|
What is the gold standard for diagnosis of Campylobacter enteritis?
|
culture
|
|
|
What is the sensitivity of C. jejuni and C. coli?
|
wide variety of antibiotics, intrinsically resistant to trimethoprim and most ≤-lactams; erythromycin and fluoroquinolones are first choices for therapy
|
|
|
What are two major late onset complications associated with Campylobacter infections?
|
Guillain-Barre syndrome and reactive arthritis
|
|
|
What is the most commonly identified antecendent to Guillain-Barre syndrome?
|
Campylobacter jejuni
|
|
|
What is a common antecedent pathogen to reactive arthritis?
|
Campylobacter
|
|
|
What pathogen is a major cause of abortions in sheep and cattle?
|
Campylobacter fetus
|
|
|
What is Campylobacter fetus?
|
major cause of abortions in sheep and cattle, serious chronic disease in immunocompromised patients and can cause systemic infection
|
|
|
What is an Campylobacter fetus virulence factor?
|
S protein-- prevents C3b binding
|
|
|
What Campylobacter is protected if it enters the bloodstream?
|
C. fetus
|
|
|
What is a danger of Campylobacter fetus infection?
|
vascular tropism
|
|
|
What did patients who drank raw liver cocktails in Mexico get?
|
Campylobacter fetus
|
|
|
What are some important features of Helicobacter pylori?
|
faint, curved, slender Gram- rods best visualized in tissues with a silver stain, oxidase+, sheathed polar flagella causing characteristic darting motility, fastidious and slow growing, requires special conditions for growth, urease+
|
|
|
What is the only known animal reservoir for H. pylori?
|
humans
|
|
|
Where does H. pylori live?
|
in gastric mucus and in close proximity (but not inside) gastric epithelial cells and in ectopic gastric mucosa (e.g. in duodenal ulcers)
|
|
|
Does H. pylori have invasive potential?
|
no. nope. none. nosiree.
|
|
|
What is always associated with H. pylor infection?
|
inflammation (but can be asymptomatic)
|
|
|
What are some of the bad things that H. pylori causes?
|
duodenal ulcer, gastric ulcer, gastric cancer, chronic and acute antral and corpus gastritis
|
|
|
What is the one negative association with H. pylori?
|
esophageal reflux
|
|
|
Does H. pylori have high or low variability?
|
high
|
|
|
How does H. pylori get its genes?
|
transformation
|
|
|
What are the main virulence factors for H. pylori?
|
urease (produces ammonia to protect bacterium from acid), binds to epithelial cells through multiple adhesions, activates IL-8 and TH1 response, also IL-1 response, 60% contain Cag pathogenicity island loosens tight junctions, Vac+ is vacuolating
|
|
|
How does H. pylori evade the acidic environment in the stomach?
|
urease
|
|
|
What does CagA do for H. pylori?
|
secreted by type IV secretion system (made by Cag pathogenicity island), binds apical junction complex (ZO) and loosens tight junctions
|
|
|
What does Vac do for H. pylori?
|
vacuolating cytotoxin that disrupts cellular organelles
|
|
|
What causes gastric cancer?
|
chronic inflammation due to H. pylori infection
|
|
|
What causes most MALT lymphomas?
|
chronic inflammation due to H. pylori infection
|
|
|
How is H. pylori diagnosed?
|
antral biopsy during endoscopy, then CLO test (for urease activity); non-invasive test is serology, also urea breath test
|
|
|
Lecture 11
|
Haemophilus influenzae
|
|
|
Is H. influenzae the cause of the flu?
|
Nope
|
|
|
What are the major human pathogens of the genus Haemophilus?
|
H. influenzae and H. ducreyi
|
|
|
What does H. influenzae infect?
|
upper respiratory tract, conjunctiva, meninges
|
|
|
What does H. ducreyi cause?
|
chancroid
|
|
|
Describe the major characteristics of Haemophilus ducreyi
|
Gram- small coccobacilli or pleomorphic rods, fastidious organism requires X (hematin) and V (NAD) factors for growth, facultative anaerobe; grows on chocolate agar, on blood agar with a Staph cross-streak, on minimal media supplemented with X and V, spread via respiratory droplets, H. influenzae type b can cause invasive disease
|
|
|
What are the diseases generally caused by H. influenzae type b (Hib)?
|
meningitis, septicemia, epiglottitis, pneumonia
|
|
|
What are the main virulence factors for Haemophilus influenzae?
|
capsule (six serotypes-- b is most important in pathogenesis), composed of polyribosyl ribitol phosphate (PRP), IgA1 protease, endotoxin (LOS), outer membrane proteins involved in iron acquisition, pili and other adhesins
|
|
|
How well do antibodies work against Haemophilus influenzae?
|
antibodies against capsule are protective, anti-PRP Abs are bactericidal and/or opsonic and natural Abs are cross-reactive with antigens produced by other bacteria such as E. coli K100
|
|
|
Why are children less than 18 months old at higher risk of H. influenzae infection?
|
children under 18 months don't have a good immune response to polysaccharides antigens alone (T-independent) or to polysaccharide only vaccine
|
|
|
What is an important possible resistance factor for H. influenzae?
|
some isolates have ≤-lactamases
|
|
|
What is the structure of the Haemophilus influenzae vaccine?
|
PRP polymer + protein
|
|
|
What is the main component of type b H. influenzae capsule?
|
polyribosyl ribitol phosphate (PRP) polymers
|
|
|
What are the two main human pathogens of the Bordetella genus?
|
B. pertussis infects the respiratory tract, causing pertussis or whooping cough; B. parapertussis causes parapertussis, which can present as mild to severe respiratory distress
|
|
|
What are the main characteristics of Bordetella pertussis?
|
Gram- small coccobacilli or pleomorphic rods, very fastidious organism and a strict aerobe, can be cultured on Bordet-Gengou Agar as bisected pearls, spread via droplets, colonizes respiratory cilia but invasion is not classically part of pathogenesis, biphasic disease
|
|
|
What bacteria is often identified using fluorescent antibodies?
|
Bordetella pertussis
|
|
|
What is the development of pertussis?
|
biphasic disease primarily seen in children <12 years old who haven't been immunized; catarrhal phase: colonization of respiratory epithelium causing local damage, paroxysmal phase: systemic intoxication with pertussis toxin (including intense coughing, comiting and convulsions)
|
|
|
What are the main virulence factors of Bordetella pertussis?
|
attachment factors: filamentous hemagglutinin (FHA), pertactin (outer membrane protein), pili (serotype specific), pertussis toxin also functions in attachment; toxins: adenylate cyclase/hemolysin, tracheal cytotoxin, pertussis toxin, LOS (lipooligosaccharide)
|
|
|
How does Bordetella increase cAMP levels in host cells?
|
adenylate cyclase/hemolysin is excreted by the bacteria, enters mammalian cells and causes cAMP production; this impairs cell function particularly in lymphocytes and phagocytes
|
|
|
What is tracheal cytotoxin?
|
tetrapeptide derived from peptidoglycan; used by Bordetella pertussis and causes cioliostasis and inhibition of DNA synthesis, eventually cell death;
|
|
|
What does pertussis toxin do?
|
blocks inhibition of AC by ADP ribosylation of Gi; increases cAMP and inhibits chemotaxis and function of neutrophils, macrophages and lymphocytes
|
|
|
What is bvg (in B. pertussis)?
|
bvg=Bordetella virulence gene locus; two component system turns on bvg in response to environmental stress; turns on every virulence factor except tracheal cytotoxin
|
|
|
What is the important phase for antibiotics to be used against Bordetella pertussis?
|
during the catarrhal phase
|
|
|
What's the story of the Bordetella pertussis vaccine?
|
used to be it had some undesirable side effects; new safer vaccine (acellular pertussis vaccine AKA aP) introduced in 1996; it is composed of subunits (e.g FHA, PTX, pertactin)
|
|
|
Lecture 10
|
Neisseria
|
|
|
Describe the main characteristics of Neisseria
|
kidney bean shaped, Gram- diplococci, oxidase positive, obligate human pathogens, vastidious organisms: need 4-8% CO2 to enhance growth, will not grow at 22∞ C (they like 30-37∞), susceptible to heat, cold and drying, highly autolytic at stationary phase, cannot tolerate free fatty acids in media, pathogenic Neisseria are piliated when isolated
|
|
|
What are good plates for growing Neisseria?
|
chocolate agar and Thayer Martin media (chocolate agar +vancomycin, colistin, trimethoprim and nystatin
|
|
|
Where do you perform a Neisseria culture?
|
at the bedside
|
|
|
What are the metabolic foods of Neisseria?
|
produce acid from sugars (e.g. glucose, maltose, lactose, sucrose) using an oxidative pathway
|
|
|
When would Thayer Martin media be used for a culture?
|
when normal flora are likely to interfere with culture and you're looking for Neisseria
|
|
|
What is unique about Neisseria metabolism?
|
produce acid from sugars using an oxidative pathway, not a fermenting pathway
|
|
|
What metabolic test differentiates between Neisseria meningitidis and Neisseria gonorrhoeae?
|
N. meningitidis can oxidize glucose and maltose to acids; N. gonorrhoeae can only oxidize glucose to acid
|
|
|
How do Neisseria invade epithelial cells?
|
stick to mucous secreting (but not ciliated) cells by pili and opa proteins, cause ciliostasis with LOS and PDG, endocytosis is directed by porins; they are transpored through the cells and egested into the basement membrane leading to massive inflammation; ciliated and non-ciliated host cells are destroyed; organisms resist killing by antibody and complement in inflammatory fluids and blood; attachment to endothelial cells follows, then dissemination of organisms into bloodstream
|
|
|
What are the main virulence factors for Neisseria species?
|
iron stealing, capsule (meningitidis), pili, porins, blocking Abs, adherence proteins, LOS, IgA protease
|
|
|
Which Neisseria species has a capsule known to be virulent? And how does it work?
|
meningitidis: capsule is acidic polysaccharide, antiphagocytic and anticomplementary, divided into 13 serogroups (A,C,B cause most disease), most capsules are composed of sialic acid, and capsule is target of protective antibody
|
|
|
What is the difference between the pili of Neisseria species?
|
meninitidis pili promote ttachment to epithelial, endothelial cells and RBCs and are necessary for transformation; gonorrhoeae pili mediate attachment to epithelial cells, adhere to columnar epithelial cells of mucosa, necessary for transformation, they're antiphagocytic and undergo antigenic variation
|
|
|
What is important about the pili of N. gonorrhoeae?
|
they adhere to columnar epithelial cells of mucosa and they undergo antigenic variation
|
|
|
Which porin is an antibody target in Neisseria?
|
Class 1 porins in N. meningitidis
|
|
|
What is the difference in blocking antibody specificity between Neisseria meningitidis and Neisseria gonorrhoeae?
|
N. meningitidis uses Class 4, no variateion, target for IgA blocking prevents IgG attachment; N. gonorrhoeae uses Rmp, antigen for production of IgG antibody that blocks killing by IgM; in both cases previous exposure to cross-reacting antigens contributes to the presence of blocking Ab
|
|
|
What is the difference in adherence proteins between N. meningitidis and N. gonorrhoeae?
|
MC uses class 5 outer membrane proteins to adhere to host cells and leukocytes; GC usese opa (opacity protein, formerly PII), promotes adherence to mucosa and PMNs and a single cell can exhibit antigenic variation
|
|
|
What does Rmp do (Neisseria gonorrhoeae)?
|
target for IgG antibody, blocks IgM
|
|
|
What does Opa do (Neisseria gonorrhoeae)? How is it related to pathology?
|
promotes adherence to mucosa and PMNs; if present in culture=opaque colony=local disease; if absent=transparent colony=disseminated gonococcal infections (DGI)
|
|
|
What is a marker of disseminated gonococcal infections?
|
lack of Opa protain (transparent colony)
|
|
|
What are Neisseria porins useful for?
|
serotyping
|
|
|
What is the important part of LPS for Neisseria?
|
lipooligosaccharide or LOS
|
|
|
What bad stuff does the Neisseria meningitidis LOS do?
|
causes cytokine release leading to local inflammation and/or toxic shock and DIC, LOS is sialylated which decreases MBL binding and complement activation
|
|
|
What bad stuff does the Neisseria gonorrhoeae LOS do?
|
damages cilia leading to sloughing, exhibits antigenic variation, target of IgM
|
|
|
Which Neisseria species has an IgA protease?
|
trick question! They both do
|
|
|
What are the diseases caused by Neisseria meningitidis?
|
meningitis, meningococcemia alone, Waterhouse Friderichsen syndrome, pneumonia (uncommon)
|
|
|
What is the key feature of meningitis caused by N. meningitidis?
|
skin lesions, start as petechiae, become purpuric and eventually necrotic (lesions occur as LOS is shipped out of cell)
|
|
|
What are the key features of meningococcemia?
|
low grade fever, skin lesions and arthritis developing over a period of days to weeks
|
|
|
What is Waterhouse-Friderichsen syndrome?
|
can be caused by Neisseria meningitidis, includes bilateral hemorrhagic destruction of the adrenal glands, fulminating DIC and shock
|
|
|
When are the peak age groups affected by meningococcal disease?
|
6-24 months and 10-20 years
|
|
|
What are host factors that increase risk of susceptivility to Neisseria bacteremia?
|
absence of bacteriocidal antibodies, production of blocking antibodies, terminal complement component (C6,7,8) deficiencies, MBL deficiency
|
|
|
How is N. meningitidis lysed by the immune system?
|
IgG to the capsule and complement
|
|
|
How is N. meningitidis transmitted?
|
nasal droplets from asymptomatic carriers
|
|
|
What are important tools for diagnosis of N. meningitidis?
|
Gram stain of CSF and culture of CSF/blood/skin lesions
|
|
|
When does serum not kill Neisseria meningitidis?
|
production of IgA blocking Ab, sialylation of LOS which decreases binding of MBL and prevents complement activation
|
|
|
Where is Neisseria meningitidis (serogroup A) endemic?
|
sub-saharan Africa
|
|
|
What is important to know about B Neisseria meningitidis?
|
>50% of cases, non-immunogenic
|
|
|
What are the two vaccines for Neisseria meningitidis?
|
quadrivalent polysaccharide vaccine (MPSV4 or Menomune) lasts for 3-5 years; meningococcal conjugate vaccine (MCV4 or Menactra) should last longer
|
|
|
What are the main treatment strategies for Neisseria meningitidis?
|
penicillins and cephalosporins (resistance found outside US), high IV dose given in case of meningococcemia or meningitis; prophylaxis of carriers or close exposure with rifampin, relatively new adjunctive therapy with rBPI21
|
|
|
Why can PCN not be used prophylactically for N. meningitidis exposure?
|
it can't get to the surface of uninflamed nasopharyngeal mucosa
|
|
|
What are the main diseases caused by Neisseria gonorrhoeae?
|
men: urethritis, epididymitis; women: cervicitis, salpingitis, and PID; rarely, disseminated gonococcal infection (DGI) characterized by polyarthralgia, tenosynovitis, dermatitis or septic arthritis. Lesions are pustular and erythematous
|
|
|
What are the main risk factors for N. gonorrhoeae transmission?
|
sexually active young adults, peaks occur in 15-24 and 25-30 age groups, causes endemic disease; production of blocking antibodies and deficiency of terminal complement components are bad
|
|
|
What is critical for diagnosis of N. gonorrhoeae?
|
men: seing GC in PMNs on Gram stain is diagnostic; for women need cervical pus culture; can do a nucleic acid hybridization
|
|
|
What is the antibody susceptibility of N. gonorrhoeae?
|
killed by IgM antibody to LOS and complement, failure of serum killing is due to production of IgG blocking antibody
|
|
|
What is the recommended treatment of N. gonorrhoeae?
|
cephtriaxone, an injectable cephalosporin, or oral cefixime or a quinolone in a single dose (avoids poor compliance); ≤-lactam resistance: plasmid-mediated ≤-lactamase and chromosomally-mediated via decreased permeability of outer membrane and/or decreased penicillin binding protein affinity (also affects tetracycline uptake)
|
|
|
Lecture 11
|
Chlamydia and Mycoplasma
|
|
|
What are the main characteristics of Chlamydia?
|
obligate intracellular parasites, prevent phagolysosomal fusion and live in the phagosome, energy parasites because they can't make ATP, import nutrients from the cytosol into the endosome with help of tubular projections on the surface of reticulate body, have little or no peptidoglycan (considered to have Gram- envelope), exist in two forms (distinct infectious or EB and reproductive or RB)
|
|
|
What types of infections are caused by Chlamydia?
|
persistent and recurrent infections; C. trachomatis causes blindness, urethritis, cervicitis and salpingitis; C. psittaci and C. pneumoniae cause pneumonia
|
|
|
What are the main approaches to laboratory diagnosis of Chlamydia?
|
Psittacosis and Lymphogranuloma Venereum (LGV) uses complement fixation to look at LPS; C. trachomatis is detected using fluorescent antibody staining of genital exudates with monoclonal antibodies against MOMP or LPS; nucleic acid hybridization techniques are widely used to detect asymptomatic genital infection in women
|
|
|
What is the mainstay of Chlamydia treatment?
|
macrolides and tetracyclines; must be used for >10 days; in non-compliant patients a long-acting macrolide (e.g. azithromycin) is drug of choice
|
|
|
What is the life cycle of Chlamydia?
|
extracellular elementary body (EB) attaches to a specific host cell receptor and undergoes parasite-specified endocytosis, remaining in the phagosome and preventing phagolysosome; EB differentiates into metabolically active reticulate bodies (RB) in 10 hours, in next 20 hours reticulate bodies multiply via binary fission and differentiate into elementary bodies, to become an elementary body the DNA must condense and disulfide bridging of the MOMP needs to occur. EBs are then released from the cell by cytolysis
|
|
|
What is the primary host of Chlamydia trachomatis?
|
humans
|
|
|
What is the shape of the Chlamydia EB?
|
round
|
|
|
What is a biovar in C. trachomatis?
|
a division used in Chlamydia based on target host cells; Biovar trachoma infects squamocolumnar epithelial cells of the eye and GU tract, causes conjunctivitis in primates; biovar lymphogranuloma venereum (LGV) infects inguinal lymph nodes and causes lymphogranuloma venereum, lethal to mice if injected intracerebrally
|
|
|
What are the major trachoma serovars of C. trachomatis?
|
A,B,C cause chonic conjunctivitis; D,E,F,G (and B,C,H,I,K) cause oculogenital diseases (e.g. urethritis, cervicitis, salpingitis and acute conjunctivitis)
|
|
|
What are the major diseases caused by C. trachomatis?
|
trachoma is leading cause of preventable blindness, main vector is common house fly; clinical course is chronic follicular conjuctivitis of childhood that progresses to conjunctival scarring, in-turned eyelashes may occur and constant rubbing can cause abrasions of the cornea; also cause STDs: persistent and recurrent genital infections that lead to scarring
|
|
|
What is the major route of host defense against C. trachomatis?
|
CMI probably controls intracellular infection but also probably contributes to scarring of the eyes or genital tract in persistent infection; system IgG is not protective, at low inoculum IgA is protective, HSP-60 may be involved in the CMI response
|
|
|
What is the primary host of Chlamydia psittaci?
|
birds-
|
|
|
Which infects humans, avian or mammalian biovar of Chlamydia psittaci?
|
avian
|
|
|
What is the agent that causes parrot fever?
|
AKA psittacosis, Chlamydia psittaci causes it!
|
|
|
What is unique about the shape of Chlamydia pneumoniae?
|
EB is pear shaped
|
|
|
What does C. pneumoniae cause?
|
pneumonia, pharyngitis and bronchitis
|
|
|
What are the main characteristics of mycoplasma?
|
among smallest of free-living organisms, complex nutritional requirements, dependent on external supplies of many precursors including nucleotides, AAs, fatty acids and sterols; resemble Gram- bacteria but lack a cell wall (PDG), bounded by single trilaminar membrane, inherently resistant to ≤-lactams (lack PDG), characteristic "fried egg" colonial morphology, can hemadsorb and hemolyse RBCs, facultative and mainly fermentative
|
|
|
What is the classic mycoplasma colony morphology?
|
fried egg
|
|
|
Why is mycoplasma intrinsically resistant to ≤-lactams?
|
they lack a bacterial cell wall
|
|
|
What does Mycoplasma pneumoniae cause?
|
tracheobronchitis with nonproductive cough and primary, atypical pneumonia in young adults and children
|
|
|
How is Mycoplasma spread?
|
droplets to the upper respiratory tract
|
|
|
How does Mycoplasma adhere to and damage host cells?
|
attaches to epithelial cells using P1 adhesin which binds to sialic acid on host cells; damages mucosa by producing H2O2 and superoxide, leads to ciliastasis and epithelial necrosis
|
|
|
What are some of the rare extrapulmonary manifestations of Mycoplasma pneumoniae?
|
myocarditis, pericarditis, encephalitis, neuropathies, rashes, tender joints and muscles, polyarthritis (may be caused by autoimmune mechanisms)
|
|
|
Describe a common autoimmune reaction that occurs due to Mycoplasma
|
IgM antibodies to I antigen on RBC membranes appear and may cause intravascular hemolysis; cold agglutinin response seen in ~60% of patients
|
|
|
What are the main immune mechanisms that control Mycoplasma infection?
|
complement-mediated lysis, anti-attachment, opsonization by polys; correlates with acquisition of serum IgG against M. pneumonia, though cell mediated immunity is not protective
|
|
|
What are some of the non-culture techniques for the identification of Mycoplasma pneumoniae?
|
complement fixation test (measures IgG and IgM), ELISA (measures IgM and IgG to P1 adhesin), antigen campture enzyme immunoassay (Ag-EIA), PCR (detects genomic DNA)
|
|
|
What is the main treatment of Mycoplasma?
|
empiric therapy to cover agents of atypical pneumonia (mainstays are erythromycin and doxycycline; long acting macrolides and quinolones are alternative agents)
|
|
|
Lecture 12
|
Anaerobic Infections
|
|
|
What kind of environment helps anaerobes thrive?
|
reducing environment
|
|
|
What kind of infection do anaerobes usually cause?
|
opportunistic-- normal inhabitants of oral cavity, vagina and gut; disease is associated with tissue injury and compromise of vasculature
|
|
|
What are some common host defenses against anaerobic infection?
|
increased redox potential usually kills them, phagocytes can ingest and kill anaerobes in healthy tissues but oxygenation of tissues is really major protection
|
|
|
What is the common clinical presentation of anaerobic infection?
|
usually present as mixed infection, facultative organisms use up the oxygen and anaerobes proliferate (facultative organisms may also provide essential nutrients), anaerobic infection causes formation of purulent abscesses: tissue breakdown, invasion by PMNs and walling off; rule of thumb: anaerobes cause infections in injuries adjacent to their normal habitat
|
|
|
Why do abscesses usually have to be drained?
|
anaerobes are reproducing and in well walled-off, poorly oxygenated abscesses PMNs can't win, so you have to drain the abscess
|
|
|
What is an important drug of choice for anaerobes? How does it work?
|
metronidazole-- must be reduced to become toxic, then inhibits DNA synthesis; resistance is very uncommon
|
|
|
What are some important characteristics of Bacteroides species?
|
Gram- baccili, nonmotile, indigenous gut flora, LPS much less toxic than Enterobacteriaceae, ferment glucose to acetate propionate and succinate; most frequently isolated cause of anaerobic infections
|
|
|
What is the most commonly isolated species causing anaerobic infections?
|
Bacteroides fragilis
|
|
|
What is the most prevalent genus of anaerobe in stool?
|
Bacteroides
|
|
|
What are some prime features of Bacteroides fragilis?
|
lives in lower GI and/or vagina, bile resistant, can survive oxygen exposure for long periods but can't grow, has polysaccharide capsule which is antiphagocytic and chemotactic, penicillin resistant, often produces Vitamin K
|
|
|
What Bacteroides species is bile resistant?
|
B. fragilis
|
|
|
What Bacteroides species can survive long periods of oxygen exposure?
|
B. fragilis
|
|
|
What are some diseases caused by Bacteroides fragilis?
|
diverticulitis, septic abortion, septic thrombosis, GI infections
|
|
|
What are some prime features of Prevotella melaninogenica?
|
usually lives in oral pharynx and GI tract and/or vagina, grows black on a special type of blood agar, virulence factors include collagenase, leukocyte inhibitory factor and a capsule, 10-25% of strains are penicillin resistant
|
|
|
What species of anaerobic bacteria grows black on a special type of blood agar?
|
Prevotella melaninogenica (formerly Bacteroides melaninogenicus)
|
|
|
What are some diseases caused by Prevotella melaninogenica?
|
lung and dental infections
|
|
|
What are some general characteristics of Fusobacterium species?
|
pale staining, slender, Gram- rods with tapered ends, normal flora of oral cavity, GI tract and vagina, do not have capsule but have very potent LPS, have butyric acid as principle metabolic end product
|
|
|
What species has a pale staining, slender, Gram- rod with tapered ends, like needles?
|
Fusobacterium
|
|
|
What is the most potent virulence factor of Fusobacteriae?
|
potent LPS
|
|
|
What does Fusobacterium necrophorum look like?
|
broad, rounded ends on Gram stain with bulges in middle of cells
|
|
|
What anaerobe causes liver abscesses?
|
Fusobacterium necrophorum
|
|
|
What are the virulence factors of Fusobacterium necrophorum?
|
leukocidin and hemolysin
|
|
|
What does Fusobacterium nucleatum cause?
|
pulmonary infections
|
|
|
What does Fusobacterium nucleatum look like?
|
Gram- rod with thin pointed ends
|
|
|
What are some main features of Peptostreptococci?
|
Gram+ anaerobic cocci that occur in short chains, live in mouth and intestine, cause brain, liver, breast, lung abscesses, can cause disease alone
|
|
|
What causes actinomycosis (chronic destructive abscesses in connective tissue)?
|
Actinomyces israelii
|
|
|
What are classic findings in the pus of infections with Actinomyces israelii?
|
sulfur granules composed of bacteria in a matrix of calcium phosphate
|
|
|
What test differentiates between Actinomyces israelii and Nocardia?
|
acid fast-- Nocardia IS
|
|
|
What are the main differences between Actinomyces and Nocardia?
|
Actinomyces: Gram+ branching rod, anaerobic, penicillin sensitive and acid fast negative; Nocardia: Gram+ branching rod, aerobic, soil organism, partially acid fast and penicillin resistant
|
|
|
What are some important characteristics of Clostridium species?
|
Gram+ rods, large and pleiomorphic, but after 48 hours cultures can stain Gram-, spore formers, if motile they have peritrichous flagella, found in soil and some are normal flora of GI tract, produce many enzymes
|
|
|
Is C. perfringens motile or not?
|
not
|
|
|
What are some enzymes commonly produced by Clostridium?
|
collagenase, protease, hyaluronidase, DNAse, lecithinase, neuraminidase, toxins
|
|
|
What is strange about Clostridium Gram staining?
|
originally Gram+, they can become Gram- after 48 hours
|
|
|
Where is C. perfringens found?
|
soil and intestine
|
|
|
What are some diseases caused by C. perfringens?
|
gas gangrene, soft tissue infections, food poisoning, abdominal infection of biliary tree, septic abortions
|
|
|
What is the spore of C. perfringens like?
|
subterminal; spores will not form on artificial culture media
|
|
|
What bacteria exhibits a double zone of hemolysis on blood agar?
|
C. perfringens
|
|
|
What are some important virulence factors for C. perfringens?
|
alpha toxin (lecithinase) (a calcium-dependent phospholipase C), enterotoxin type A (heat labile)
|
|
|
What does alpha toxin (C. perfringens) do?
|
causes lysis of RBCs and other cells
|
|
|
What does enterotoxin type A (C. perfringens) do?
|
causes acute food poisoning (presents as self-limited gastroenteritis), heat labile
|
|
|
What does Clostridium difficile cause?
|
25% of diarrhea associated with antibiotic therapy, 95% of cases of pseudomembranous colitis, growing concern about increase in serious diarrhea and colitis by C. difficile
|
|
|
Where can one often contract a C. difficile colitis?
|
a hospital
|
|
|
What kind of spore does C. difficile have?
|
subterminal
|
|
|
What are two toxins necessary for C. difficile to have enterotoxicity?
|
toxin A (enterotoxin) and B (cytotoxin) bind to receptors on intestinal epithelial cells, glucosylate Rho proteins and disrupt focal adhesions between cells, leading to both massive secretion of fluid (diarrhea) and an acute inflammatory response
|
|
|
How does antibiotic therapy induce C. difficile infection?
|
C. difficile often acquired in hospital and colonizes the GI tract; antibiotics can alter the balance of GI flora and facilitate overgrowth of C. difficile
|
|
|
What are some especially risky antibiotics that might cause C. difficile diarrhea or colitis?
|
broad spectrum antibiotics like penicillins, cephalosporins and clindamycin
|
|
|
What unrelated medication increases the risk of infection by C. difficile in patients taking broad spectrum antibiotics?
|
PPIs such as omeprazole
|
|
|
How is C. difficile disease diagnosed?
|
endoscopy and a toxin assay of stool
|
|
|
What are the treatments for C. difficile?
|
metronidazole or oral vancomycin
|
|
|
Lecture 13
|
Toxigenic Bacteria
|
|
|
What is a common target of exotoxins?
|
host gangliosides
|
|
|
What is a toxoid and what is an example of one?
|
a molecule that resembles a toxin but is used immunogenically to create a protective antibody response against a toxin. Examples include diptheria and tetanus
|
|
|
Where is cholera toxin encoded?
|
on a lysogenic phage
|
|
|
What are some general characteristics of Vibrio cholerae?
|
short, curved, motile, Gram- rod, two serotypes associated with cholera in humans: O139 and O1, which has two biotypes (classical and El Tor)
|
|
|
What is the mechanism of action of cholera toxin?
|
5 B subunits bind to host membrane and make a pore for the A subunit; A subunit ADP ribosylates alpha subunit of Gs, knocking out innate GTPase activity!íAC keeps producing cAMP and Cl- leaves cell followed by Na+ and H2O and a watery, electrolyte diarrhea is formed
|
|
|
How does Cholera present?
|
sudden onset nausea+vomiting, profuse watery diarrhea, rapid loss of bodily fluids with circulatory collapse, without intervention, death usually follows from dehydration within 24 hours
|
|
|
What are two good E. coli toxins?
|
Labile Toxin (LT) and Stable Toxin (ST)
|
|
|
What is the mechanism of action of LT (E. coli)?
|
B subunits bind and A subunit ADP ribosylates Gs± to stimulate AC to produce cAMP and cause secretion of Cl- Na+ and H2O; LT must be cleaved; it is not secreted
|
|
|
How are LT and cholera toxin related?
|
evolutionarily related (80% homology), but LT is less severe
|
|
|
Why is LT less severe than cholera toxin?
|
LT is not secreted, LT must be cleaved by host cell protease, but V. cholerae produces its own protease
|
|
|
What diseases does LT cause?
|
traveler's diarrhea and diarrhea in infants
|
|
|
Where is ST encoded?
|
plasmid
|
|
|
What is the mechanism of action of ST?
|
binds to guanylate cyclase C on brush border, elevating intracellular cGMP and causing Cl- secretion
|
|
|
Why might E. coli induced disease (through ST toin) be worse in children?
|
infants have more receptors
|
|
|
Where is pertussis toxin encoded?
|
chromosomally encoded, under control of bvg
|
|
|
What is the mechanism of action of pertussis toxin?
|
blocks inhibition of AC by ADP ribosylation of Gi, net effect is increased cAMP
|
|
|
What protein does B. pertussis make that mimics a host protein to screw them up?
|
adenylyl cyclase enters mamallian cells, inhibits host inflammatory mechanism by screwing up cAMP cascades
|
|
|
Should you get vaccinated against B pertussis?
|
apparently, yes.
|
|
|
Where is diptheria toxin encoded?
|
phage encoded, gene "tox" resides on a lysogenic phage (B phage)
|
|
|
What diseases does diptheria toxin cause?
|
infects throat, occasionally skin wounds
|
|
|
When does Corynebacterium diptheriae release diptheria toxin?
|
under pressure of iron restriction
|
|
|
How does diptheria toxin work?
|
synthesized as single AA chain (must be cleaved to work), A is active chain, B mediates entry; toxin catalyses ADP ribosylation of EF2, knocking out host protein synthesis
|
|
|
How does diptheria toxin present clinically?
|
necrosis of posterior pharynx; if absorbed systematically, produces heart toxicity that presents as heart failrue
|
|
|
Where is exotoxin A (P. aeruginosa) encoded?
|
chromosomally encoded, under control of las R
|
|
|
When is exotoxin A produced?
|
in response to iron restriction
|
|
|
What is the mechanism of action of exotoxin A?
|
catalyzes ADP ribosylation of EF2, knocking out host protein synthesis; not the only virulence factor and must unfod for activity
|
|
|
exotoxin A has convergent evolution with what other toxin?
|
diptheria
|
|
|
Where is the Tetanus toxin of Clostridium tetani encoded?
|
plasmid; same found in all strains
|
|
|
What is the mechanism of action of tetanus toxin?
|
terminal spores inoculated into injury, as redox potential drops S. tetani can gow; toxin is also a metalloprotease, causes disinhibition of motor neurons and overstimulation causes spastic paralysis
|
|
|
Why is an individual who has had a tetanus infection not immune in the future?
|
not enxough toxin
|
|
|
What organism makes botulism toxin?
|
Clostridium botulinum
|
|
|
What is the mechanism of action of botulinum toxin (BoNT)?
|
metalloprotease, binds to presynaptic receptors and is taken up, blocks ACh release irreversibly, death occurs from respiratory failure
|
|
|
Will an individual make an antibody response to botulism toxin?
|
no.
|
|
|
What causes floppy baby syndrome?
|
children under 1 year old consume honey but Clostridium botulinum spores are there); as low levels of toxin are produced, child develops progressive muscular weakness and poor motor development
|
|
|
What is wound botulism?
|
when tissue is colonized by C. botulinum with absorption of toxin from the wound site; infection is usually inapparent
|
|
|
What is wound botulism most commonly associated with in the US?
|
drug abuse
|
|
|
What does Bacillus anthracis look like?
|
Gram+ rod that produces spores, nonmotile and grows well on blood aga
|
|
|
What are the three major anthrax syndromes?
|
cutaneous (most common), inhaled (most lethal) and gastrointestinal
|
|
|
Where are anthrax virulence factors encoded?
|
two plasmids: one for antiphagocytic capsuel and the other carrying the toxin genes
|
|
|
What are the three B. anthracis exotoxins that cause disease?
|
edema factor (EF)- calmodulin-dpependent adenyly cyclase; lethal factor (LF)- metalloprotease that cleaves MAPK 1 and 2; protective antigen (PA) is in protective anthrax vaccines, couples with edema factor and lethal factor to promote their entry into cells
|
|
|
What is anthrax vaccine abdsorbed (AVA)?
|
the only licensed human anthrax vaccine int he US-- contains crude preparation of protective antiben;
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Lecture 17
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Molecular Mimicry
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What are classic autoimmune diseases resulting from molecular mimicry?
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acute rheumatic fever (ARF) and Guillain-Barre syndrome (GBS)
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What is the necessary preceeding infection to acute rheumatic fever?
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pharyngeal infection with GAS
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What are major risk factors for developing ARF?
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high Ab titer to GAS, family history, previous episode of ARF, certain MHC II aleles (HLA-DR4 and HLA-DR2)
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What is the primary suspect for molecular mimicry in GAS?
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M protein, ±-helical structure matches myosin, collagen, tropomyosin
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Why is it possible that a vaccine against M protein (GAS) may never be made?
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it has a high likelihood of generating cross-reacting human antibodies
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What are the diagnostic criteria for ARF?
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Jones criteria: 2 major (carditis, polyarthritis, Sydenham's Chorea, Erythema marginatum, Subcutaneous nodules) or 1 major and 2 minor (fever, arthralgia, previous ARF or rheumatic disease, acute phase reactions, prolonged P-R interval); all must be supported by evidence of GAS infection
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What are ways of assessing for a previous strep infection?
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increased antistreptolysin (ASO) titer or other antibody titers, Hx of recent scarlet fever, positive throat culture for GAS, anti-DNAse B, antihyaluronidase, streptokinase
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How does ARF-caused carditis look?
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most severe manifestation, wide range, valves affected=mitral>aortic>tricuspid; valve damage leads to insufficiency or stenosis and heart failure
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When do most people develop rheumatic heart disease?
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only after multiple episodes of ARF
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What is characteristic of the arthritis induced by ARF?
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migratory joint pain and swelling, two or more are affected (usually large joints of the extremities), pain responds to aspirin and NSAIDs, heals with no permanent disability
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What is Syndenham's Chorea (St. Vitus dance)?
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gradual onset with long latent period, characterized by sudden, aimless, irregular movements accompanied by muscular weakness/emotional instability; disappears during sleep
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What is erythema marginatum?
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evanescent pink rash with clear center, pathognomic for ARF; has round or serpiginous margins and never appears on the face; monly on trunk or proximal extremities, and only occurs in children
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What are the subcutaneous nodes and Aschoff bodies?
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nodules are small, pea-sized, painless swellings over bony prominences (only seen with severe carditis), nodules consist of spindle shaped interstitial aggregate for large mononuclear cells surrounding the fibrosis, Aschoff bodies are found throughout the body (typically in heart) and are pathognomonic for RHD
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What factors indicate an acute phase reaction?
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change in erythrocyte sed rate, presence of C-reactive protein
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What is the treatment of ARF?
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PCN is mainstay, erythromycin can be given to those with PCN allergies; in patients with acute carditis corticosteroids are often prescribed to shut down inflammation injury
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What is a good way to prevent ARF?
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prophylaxis: treat GAS pharyngitis with PCN for 10 days; since recurrences are common prophylactic antibiotics need to be given
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What is Guillain-Barre (GBS)?
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acute polyneuropathy that can lead to motor and sensory deficits
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What are some Sx of GBS?
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rapid onset symmetrical limb weakness, loss of deep tendon reflexes, variable sensory loss and ascending neuropathy
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What organisms cause GBS?
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viruses: (cytomegalvirus, epstein barr, varicella zoster); vaccines e.g. rabies vaccine; bacteria (Mycoplasma pneumoniae and Campylobacter jejuni
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What is the most common antecent infection for GBS?
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Campylobacter jejnui
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What serotype of GAS is associated with higher likelihood of developing GBS
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O19
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What disease is more likely to be isolated from patients wtih serotype O19 GBS?
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Miller-Fischer variant (Sx include ophthalmoplegia, ataxia and areflexia
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What is a potential molecule causing molecular mimicry in E. cole?
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O19 and others contain neuraminic acid (AKA sialic acid) in the O side chain of LPS; antibodies raised against them are thought to cross react with peripheral nerves; many serotypes also have gropus mimicking the polar head group of gangliosides; biopsies of GBS patients show C3 or Ab-C3 bound to Schwann cells
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What important clinical problem may be linked to Chlamydia infection?
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atherosclerotic plaques
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What are the ≤-lactam antibiotics?
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antibiotics that share a ≤-lactam ring; include penicillins, cephalosporins, monobactams, carbapenems
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