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40 Cards in this Set
- Front
- Back
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The virulence of an organism depends on:
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The presence of certain cell structures and on bacterial exotoxins and endotoxins
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Flagella structure and virulence.
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Protein filaments that extend like long tails from the cell membranes of certain gram-positive and gram-negative bacteria. Attaches to membrane(s) via basal body.
Vibrio (gram - enteric bacteria) has one long polar flagella, e.coli (gram - enteric) has petrichous flagella all around the cell, and shigella (gram - enteric) has no flagella. |
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Pili structure and virulence
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Pili are much shorter than flagella and do not move. Can serve as adherence factors (aka adherins) which can be vital to their ability to cause disease.
Neisseria gonorrhea (only group of gram - cocci) has pili that allow it to bind to cervical cells and buccal cells to cause gonorrhea. E. coli and campylobacter jejuni require adhesins to bind intestinal epithelium. Bordetella pertussis uses adhsin to bind to ciliated respiratory cells and cause whopping cough. W/o these pili, they can't infect by grabbing onto host. |
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Capsule structure and virulence
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Protective walls that surround cell membranes of gram + and gram - bacteria. Usually composed of simple sugar moieties which coat outer wall. Bacillus anthracis (gram + facultative anaeroe) is unique in that its capsule is composed of amino acid residues!
Capsules enable bacteria to be more virulent because macrophages and neutrophils are unable to phagocytize the encapsulated buggers. Colonies w/ capsule known as smooth and w/o known as rough. Smooth injected into mouse will kill but rough will not. |
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Tests to visualize bacterial capsules under microscope:
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1. India ink (stain is not taken up by capsule, allows capsule to appear as transparent "halo" around cell. Primarily used to identify crytococcus.)
2. Quellung rx. (The bacteria are mixed with ABs that bind to the capsule. When antibodies bind, the capsule swells with H20 and can be visualized under microscope. |
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The process of antibody binding to capsule--helping macrophages and neutrophils bind to and engulf the encapsulated bacteria is known as :
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opsonization.
Ex. a vaccine against streptococcus pneumoniae contains antigens from the 23 most common types of capsules. |
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Endospores
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Endospores are formed by only 2 genera of bacteria, both of which are gram +: Aerobic "bacillus" and anaerobic "
"clostridium." Endosporse are metabolically dormant, resistant to heat (boiling), cold, drying, and chemical agents. They have a multi-layed protective coat: A) Cell membrane B) A thick peptidoglycan mesh C) Another cell membrane D) A wall of keratin-like protein E) An outer layer called the "exosporium" They can lie dormant for years. Surgical instruments are heated in an autoclave in order to ensure the destruction of Clostridium and Bacillus spores. The spore can become active again when exposed to a favorable nutrient or environment |
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Spore structure
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From innermost to outermost:
A) Cell membrane B) A thick peptidoglycan mesh C) Another cell membrane D) A wall of keratin-like protein E) An outer layer called the "exosporium" |
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Facultative Intracellular Organisms.
(a) Mechanism (b) Organisms |
(a) mechanism: These bacteria can survive in macrophages and neutrophils. They inhibit phagosome-lysosome fusion, thus escaping the host's deadly hydrogen peroxide and superoxide radicals.
b) Organisms include: 1. Listeria monocytogenes (-) 2. Salmonella typhi (- enteric rod) 3. Yersinia (- rod) 4. Francisella tularensis (- rod) 5. Brucella (- rod) 6. Legionella (- rod) 7. Mycobacterium (acid fast) |
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Exotoxins
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Proteins that may cause disease manifestations. Released by all major gr+ genera except Listeria monocytogenes (produces endotoxin).
Gram/neg bacteria such as Vibrio cholera, E. Coli, etc. can secrete exotoxins. Severe diseases caused by exotoxins: anthrax, botulism, tetanus, and cholera. |
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Neurotoxins
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Neurotoxins are a subclass that active on nerve or motor endplates--inducing paralysis--such as tetanus and botulinum toxin.
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Enterotoxins
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Enterotoxins are exotoxins that act on the GI tract to cause diarrhea. Enterotoxins inhibit NaCl resorption, activate NaCl secretion, or kill intestinal epithelial cells. (water tends to move along concentration gradient, so water is moving OUT)
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Enterotoxins cause the following 2 disease manifestations:
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1. Infectious diarrhea: Bacteria bind to GI and contiously release enterotoxin locally. Diarrhea continues until host immune system, antibiotic killing, or patient death.
(Ex: Vibrio cholera, E. Coli, Campylobacter, and Shigella--all gram/- rods) 2) Food poisoning: Bacteria actually release their enterotoxin into the food. The ingestion of the food can result in diarrhea and vomiting for <24hrs. Ex: Bacillus cereus and Staph aureus. |
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Pyrogenic exotoxins and examples of bacteria that utilize them.
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Stimulate the release of cytokines and can cause rash, fever and toxic shock syndrome.
Ex: Staphylococcus aureus and Streptococcus pyogenes |
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Tissue invasive exotoxins
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Allow bacteria to destroy and tunnel through tissues. These include enzymes that destroy DNA, collagen, fibrin, NAD, red blood cells, and white blood cells
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Miscellaneous Exotoxins
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Which are the principle virulence factors for many bacteria, can cause disease unique to the individual bacterium. Often the exact role of the exotoxin is poorly understood.
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Clostridium tetani:
toxin, its mechanism, effects, and notes |
Notes: tetanospasmin (tetanus toxin)
Mechanism: H (Heavy) subunit: binds to neuronal gangliosides. L (Light) subunit: blocks release of inhibitory neurotransmitters (glycine, GABA) from Renshaw inhibitory interneurons. Results in: Tetanus (continuous motor neuron activity. Uncontrolled muscle contractions with lockjaw and tetaic paralysis of respiratory muscles). 1. Vaccine: Formalin inactivated tetanus toxin--part of DPT vaccine. * diptheria * pertussis * tetanus 2. Toxin gene carried on plasmid |
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Clostridium botulinum:
toxin, its mechanism, effects, and notes |
Toxin: Botulinum toxin
Mechanism: Inhibits acetylcholine release from motor neuron endplates at NMJ Results: botulism, flaccid paralysis with respiratory muscle paralysis Notes: Its the most potent exotoxin. Toxin obtained by lysogenic conversion |
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Vibrio cholerae.
What enterotoxins does it utilize, effects on intestinal wall (mechanism), results, and additional notes |
enteroToxin: choleragen
Mechanism: (Five B subunits): which bind to GM1 gangliosides on intestinal cell membranes. (Two A subunits): Carry out the ADP-ribosylation of the GTP-binding protein. This activates membrane associated adenylate cyclase, which converts ATP to cAMP. Elevated levels of cAMP induces the secretion of NaCL and inhibits reabsorption of NaCl. Results: Cholera: increasing cyclic AMP levels result in increased intraluminal NaCl, which osmotically pulls fluid and electrolytes into the intestinal tract. This causes diarrhea and dehydration. Notes: Death by dehydration |
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1. E coli
2. Campylobacter jejuni 3. Bacillus cereus What enterotoxins do they utilize, effects on intestinal wall (mechanism), results, and additional notes |
enteroToxin: E. coli heat labile toxin (LT)-- which is similar to choleragen
Mechanism: (Five B subunits): which bind to GM1 gangliosides on intestinal cell membranes. (Two A subunits): Carry out the ADP-ribosylation of the GTP-binding protein. This activates membrane associated adenylate cyclase, which converts ATP to cAMP. Elevated levels of cAMP induces the secretion of NaCL and inhibits reabsorption of NaCl. Results: cholera-->increasing cAMP levels result in increased NaCL in lumen and secondary diarrhea and dehydration. Notes: Death by dehydration |
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1. E. coli
2. Y. enterocolitica What enterotoxins do they utilize, effects on intestinal wall (mechanism), and results |
Enterotoxin: No effect on concentration of cAMP. Rather, it binds to a receptor on the intestinal brush border and activates guanylate cyclase to produce cGMP. This results in inhibition of resorption of NaCl.
Results: Increasing cyclic GMP levels inhibits NaCl resorption by intestinal epithelial cells. This results in increased osmotic pull of fluid and electrolytes into the intestinal tract, causing diarrhea. |
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1. Shigella dysenteriae
2. Enterohemorrhagic E. Coli 3. Enteroinvasive E. Coli What enterotoxins do they utilize, effects on intestinal wall (mechanism), results, and additional notes |
Toxins:
1) Shiga toxin-- 2) Shiga-like toxin (When "shiga-toxin" is released by a bacteria other than Shigella) Mechanism: Five B subunits: Binds to intestinal epitheleial cells. A subunit: Inhibits protein synthesis by inactivating the 60S ribosomal subunit. This kills intestinal epithelial cells. Results: Shiga toxin kills absorptive intestinal epithelial cells, resulting in sloughing off of dead cells and poor absorption of fluid and electrolytes from the intestinal tract. Notes: 1. Bloody diarrhea. 2. May be responsible for hemolytic-uremic syndrome. 3. Inhibits protein synthesis in a manner analogous to the antiribosomal antibiotics (erythromycin, tetracycline, etc.) |
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Staphylococcus aureus
What enterotoxins does it utilize, results and notes |
Enterotoxin: Staphylococcal heat stable toxin
Results in: Diarrhea and vomiting that lasts for less than 24 hours. Notes: Toxins are deposited on food colonized with toxin-producing Staphylococcus |
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Bacillus cereus
What enterotoxins does it utilize, results and notes |
Enterotoxin: heat stable toxin
Results in: vomiting that lasts for < 24 hrs. Limited diarrhea. Notes: (1) B. cereus endospores survive low temperature cooking. Then, this bacteria grows and deposits this toxin on food. 2) B. cereus can also produce food poisoning by secretion of a heat labile enterotoxin (similar to that of E. Coli) |
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Streptococcus pyogenes (Group A streptococci)
What pyrogenic toxins are released? Mechanism of food poisoning? Results in? Notes: |
Pyrogenic toxins: Streptococcus pyrogenic toxin.
Food poisoning: Activates the endogenous mediators of sepsis such as cytokine interleukin-1. Results in: Scarlet fever Notes: Obtains exotoxin from a temperature bacteriophage by lysogenic conversion. |
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Staphylococcus aureus
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Pyrogenic toxins: Toxic shock syndrome toxin (TSST-1)
Mechanism: Activates the endogenous mediators of sepsis, such as the cytokin IL-1. Results in: Toxic shock syndrome (fever, rash, desquamanation, diarrhea, hypotension/shock) Notes: Streptococcus pyogenes can also cause toxic shock syndrome. |
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Streptococcus pyogenes
What tissue invasive toxins does it utilize, their mechanism, results in? |
Tissue invasive toxins include:
1. Hemolysins/streptolysin O and S (which lyses red blood cells) 2. Streptokinse (which activates plasminogen to lyse fibrin clots) 3. DNAases (Hydrolyzes DNA) 4. Hyaluronidase (which breaks down proteoglycans) 5. NADase (which hydrolyzes NAD) Results in: Tissue destruction: (aka abscesses, skin infections, and systemic infections) |
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Staphylococcus aureus:
What tissue invasive toxins does it utilize, their mechanism, results in? |
Tissue invasive toxins (include many of the tissue invasive released by streptococcus pyogenes, but also...)
1. Lipases (hydrolyzes lipids 2. Penicillinase (destroys penicillins) 3. Staphylokinase (activates plasminogen to lyse fibrin clots) 4. Leuokocidin (Lyses white blood cells) 5. Exfoliatin (Epithelial cell lyses) 6. Factors that bind complement (cripples host complement defense). Results in: Tissue destruction (aka absceesses, skin infections, and systemic infection0 2. Exfoliation is responsible for scalded skin syndrome in infants. |
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Clostridium Perfringens
What tissue invasive toxins does it utilize, their mechanism, results in? |
Tissue invasive toxins: More than 12 lethal toxins named by Greek letters: Alpha toxin (lecithinase) is the most important (and the most lethal).
Mechanism: Alpha toxin: lecithinase hydrolyzes lecithin in cell membranes, resulting in cell death. Results: Tissue destruction and gas gangrene. |
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Bacillus anthracis
What miscellaneous exotoxins are relased? The mechanism of the toxin? results in? additional notes? |
exotoxins:
Anthrax toxin (3 components:) 1. edema factor (EF) 2. Lethal factor (LF) 3. Protective Antigen (PA) mechanism: PA binding (B) subunit, which allows entry of EF into target cell. EF (a subunit) a calmodulin-dependent adenylate cyclase, increases cAMP, which impairs neutrophil function and causes massive edema (disrupts water hemostasis) 3. LF- is a zinc metalloprotease that inactivates protein kinase. This toxin stimulates the macrophage to release tumor necrosis factor alpha and IL-1beta , which contributes to death in anthrax. results in : Anthrax -edema factor is an extracellular adenylate cyclase which gets internalized by "defensive" phagocytic cells. Adenylate cyclase is activated by calmodulin, increasing the concentration of cAMP within neutrophils and macrophages. This inhibits their ability to phagocytose bacteria. Notes: 1. All 3 components required for toxin activity. 2. PA is the A (action) subunit and EF is the B (binding) subunit of the anthrax toxin. |
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Corynebacterium diptheriae
What miscellaneous exotoxins are relased? The mechanism of the toxin? results in? additional notes? |
exotoxin: diptheria toxin
Mechanism (An A-B toxin). The B subunit binds to heart and neural tissue. The A subunit: ADP ribosyltes elongation factor (EF2) thereby inhibiting translation of human mRNA into proteins. Results in: Diptheria (Myocarditis, peripheral nerve palsies, and CNS effects) Notes: 1. This exotoxin can be considered a "human antibiotic" as it inhibits protein synthesis just as tetracycline and erythromycin inhibit protein synthesis in bacteria. 2. Vaccine: Formalin treated diptheria toxin part of DPT vaccine (diptheria, pertussis, and tetanus) 3. Obtains exotoxin from a temperate bacteriophage by lysogenic conversion. |
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Bordatella pertussis
What miscellaneous exotoxins are relased? The mechanism of the toxin? results in? additional notes? |
Exotoxins: Utilizes 4 toxins.
1. Pertussis toxin (AB): B binds to target cells, and A inhibits phagocytosis--activates membrane G proteins to activate membrane bound adenylate cyclase, increasing cAMP levels, and inhibiting macrophage and neutrpohil phagocytosis. 2. Extracytoplasmic adenylate cyclase: is similar to bacillus anthracis edema factor, which impairs chemotaxis and phagocytosis 3. Filamentous hemaglutinin: allows binding to ciliated epithelial cells. 4. Tracheal cytoxin: damages respiratory epithelial cells. Results in: Whooping cough Notes: Vaccine DPT 1. Diptheria 2. Pertussis (heat killed, whole bacteria used in U.S.) 3. Tetanus |
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Clostridium Difficile
What miscellaneous exotoxins are relased? The mechanism of the toxin? results in? additional notes? |
Exotoxins: Toxin A and Toxin B. Toxin A causes fluid secretion and mucosal inflammation, leading to diarrhea. Toxin B: cytoxic to colonic epithelial cells.
Results in: Pseudomembraneous enterocolitis: colonic inflammation, with pseudomembrane formation. Clinically: diarrhea (often bloody), fever, and abdominal pain. Additional notes: antibiotic-associated diarrhea |
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Pseudomonas aeruginosa:
What miscellaneous exotoxins are relased? The mechanism of the toxin? results in? additional notes? |
exotoxins: Pseudomonas exotoxin A
Mechanism: Toxin inhibits protein synthesis by inhibiting elongation factor 2 (EF2) : same mechanism as diptheria toxin Notes: Note that diptheria as the same action as pseudomonas exotoxin A, but they have different targets: 1. Exotoxin A: liver 2. Diptheria toxin: heart |
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A-B toxins
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Exotoxin subunits in Bacillus anthracis, clostridium botulinum, clostridium tetani, corynebacterium diptheriae, and Vibrio cholera.
2 polypeptide subunits bound by disulfide bridges. B is "binding" which binds to the target cell and "A" is for "action" which enters the cell and exerts toxic effect. |
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Endotoxin mechanism
How does it differ from exotoxin? |
Endotoxin is Lipid A (a piece of the outer membrane of lipopolysaccharide--LPS).
Toxic/released when bacteria cell lyses and sometimes released from alive bacteria. (this can result in worsening of a patient's condition with a gram neg. infxn when antibiotics are introduced. Endotoxin differs from exotoxin inthat it is not a protein excreted from cells, but rather is a normal part of the outer membrane that sort of sheds off, especially during lysis. |
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Endotoxin is ONLY present in gram-negative bacteria with one exception:
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Listeria monocytogenes, (a gram positive bacteria) has endotoxin
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Sepsis
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Sepsis refers to bacteremia that causes a systemic immune response to the infection. This response can include high or low temperature, elevation of WBC count, and fast heart rate.
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Septic Shock
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Sepsis that results in dangerous drops in blood pressure and organ dysfunction is called septic shock. It is also referred to as "endotoxic shock" because endotoxin often triggers the immune response that results in sepsis and shock.
Since gram-positive bacteria and fungi can also trigger this adverse immune response, the term septic shock is more appropriate and inclusive. |
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Most potent endogenous mediator of sepsis is:
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TNF (or cachetin). TNF triggers IL-1 release from macrophages and endothelial cells, which in turn triggers the release of other cytokines and prostaglandins.
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