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46 Cards in this Set
- Front
- Back
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Family Neisseriaceae includes which three genera and what characteristics do they all share?
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(1) Neisseria (major)
(2) Kingella (3) Eikenella - Aerobic - Gram-negative cocci - Usually seen in pairs (diplococcus) with the adjacent sides flattened. |
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Two significant human pathogens in Neisseria genera include?
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(1) N. gonorrhoeae - gonorrhea = HIGH prevalence & LOW mortality
(2) N. meningitidis - bacterial meningitidis = LOW prevelance & HIGH mortality *Other species: parasites or comensals on mucosal surfaces; disease usually associated with opportunistic infections in compromised patients. |
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N. gonorrhoeae
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- aerobic, gram-negative coccus
- usually seen as diplococcus - cannot grow anaerobically unless low [ ] of alternative e- acceptor nitrite present - pili to adhere to eukaryotic cells - no capsule - lipooligosaccharide (LOS) - all are oxidase positive - most are catalase positive - oxidizes glucose to acid - very fastidious for growth - require cystine - grows on chocolate agar but not on blood agar |
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Three characteristics of lipooligosaccharides (LOS) present in N. gonorrhoeae
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(1) Highly branched basal oligosaccharide structure and absence of repeating O-antigen subunits
(2) Gonococcal LPS is referred to as LOS (3) Gonococci characteristically release outer membrane fragments (blebs) during growth -- These blebs contain LOS and may have a role in pathogenesis |
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Infectious sites of Gonorrhea (aka "the clap")
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- superficial mucosal surfaces lined w/ columnar epithelium [cannot infect ciliated cells]
- areas most frequently involved: (a) cervix, (b) urethra, (c) rectum, (d) pharynx, (e) conjunctiva - 2nd most common reported STD in U.S. [chlamydia most reported] |
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Symptoms of Gonorrhea & Ways Men/Women Transmit the Infection
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Most common symptom of uncomplicated gonorrhea: discharge from scanty, clear/cloudy fluid => copious and purulent
- Dysuria = painful urination - 2-5 day incubation period Men w/ asymptomatic urethritis are important reservoir for transmission (asymptomatic men and those who ignore symptoms = increased risk for complications) Endocervical infection: most common form in women - vaginal discharge and sometimes dysuria (b/c of coexistent urethritis) - ~50% of women are asymptomatic *occurs naturally only in humans (no other known reservoir) |
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What does disseminated infections of gonorrhea result from?
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Gonococcal Bacteremia
- asymptomatic infections of the pharynx, urethra, or cervix often precede bacteremia - most common form: dermatitis-arthritis syndrome - causes endocarditis or meningitis, but rarely - gonococci may ascend from the endocervical canal through the endometrium to the fallopian tubes and ultimately to the pelvic peritoneum, resulting in endometritis, salpingitis, and finally, peritonitis (a) pelvic and abdominal pain, fever, chills, and cervical motion tenderness (b) referred to as pelvic inflammatory disease (PID) (c) PID can be caused by other organisms (e.g., Chlamydia trachomatis) (d) as many as 15% of women with uncomplicated cervical infections may develop PID (e) complications include an increased probability of infertility and ectopic pregnancy |
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Pathogenesis of uncomplicated gonorrhea
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- only infect non-ciliated cells
- immune system mostly responsible for cell damage that occurs - LOS stimulates release of pro-inflammatory cytokines (TNF-alpha) - gets into lumen across mucosal surface |
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Gonococcal virulence factors
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- major porin protein of outer membrane (PorB) is a candidate invasin and interfers w/ degranulation of neutrophils
- extracellular IgA1 proteases - efficient utilization of transferrin-bound Fe and lactoferrin-bound iron - one or several outer membrane proteins called Opa proteins (a) undergo phase variation (b) usually found on cells from colonies possessing an opaque phenotype (O+) (c) at any one time, a gonococcus may express zero, one, or several different Opa proteins (d) each strain has 10 or more genes for different Opas - gonococci are highly autolytic and release peptidoglycan fragments during growth -- these fragments, released by bacterial and/or host peptidoglycan hydrolases, are toxic for fallopian tube mucosa and may contribute to the intense inflammatory reactions characteristic of gonococcal disease |
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Immunology and Gonorrhea
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- infection with N. gonorrhoeae stimulates both mucosal and systemic antibodies
- major antibody response (predominantly IgG3) against surface proteins (mainly pilin, Opa) and LOS. - antibody to LOS activates complement, releasing C5a with a chemotactic effect on neutrophils - LOS stimulates release of TNFα (pro-inflammatory) - PorB interfers with degranulation of neutrophils and a variant (PIA) renders bug resistant to killing by complement - prior infection doesn't prevent re-infection (no immunity due to antigenic variation in pilin and PorB proteins, phase variation of pilin expression) |
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Gonorrhea Treatment
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- Since 1993, fluoroquinolones (i.e., ciprofloxacin, ofloxacin, or levofloxacin) used frequently to treat gonorrhea b/c of their high efficacy, ready availability, and convenience as a single-dose, oral therapy
- But, recently resistance has been increasing and CDC no longer recommends use of fluoroquinolones for the treatment of gonococcal infections and associated conditions such as pelvic inflammatory disease (PID) - cephalosporins: only class of drug still recommended and available for the treatment of gonorrhea - sex partner(s) exposed to infection within 30 days should have culture taken and be given prophylactic treatment - gonorrhea is still a treatable disease - ophthalmia neonatorum: treat infections in new born eyes with 1% silver nitrate or 1% tetracycline or 0.5% erythromycin |
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N. meningitidis
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- has a polysaccharide capsule (as opposed to N. gon which doesn't)
(a) capsule is antiphagocytic and an important virulence factor (b) meningococcus - 13 serogroups based on antigenic capsule polysaccharide (a) serogroups A, B, C, X, Y, and W135 are associated with menigococcal disease (b) majority of cases in Europe and U.S. are serogroup B and C |
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Bacterial meningitis most commonly caused by these three organisms
What areas do meningococci commonly inhabit? |
(1) Haemophilus influenzae type b
(2) Neisseria meningitides [meningococcal meningitis] (3) Streptococcus pneumoniae [pneumococcal meningitis] - meningococci are common inhabitants of human nasopharynx (w/o causing detectable disease) -- 5 and 30% of normal individuals are carriers at any given time, yet few develop meningococcal disease |
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Meningococcal Meningitis
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- infection begins as meningococcemia
(a) mildest form is a transient bacteremic illness characterized by a fever and malaise (b) symptoms resolve spontaneously in 1 to 2 days - acute meningococcemia is more serious and is often complicated by meningitis - manifestations of meningococcal meningitis are similar to acute bacterial meningitis caused by other organisms (a) chills, fever, malaise, and headache are usual manifestations of infection (b) headache, vomiting, and rarely, papilledema may result from increased intracranial pressure (c) onset of meningococcal meningitis may be abrupt or insidious |
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Pathogenesis of Meningococcus
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- antiphagocytic polysaccharide capsule
- LOS: lipooligosaccharide, ie same as LPS but with a shorter O-side chain - pili and other outer membrane components mediate attachment to the non-ciliated columar epithelial cells of the nasopharynx - invasion of the mucosal cells occurs by a mechanism similar to that observed with gonococci - events involved after bloodstream invasion are unclear and how the meningococcus enters the central nervous system is not known |
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Meningococcal Epidemiology
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- carriage rates highest in older children and young adults, but attack rates are higher in younger children
-- low incidence of disseminated disease following colonization suggests that host rather than bacterial factors play an important role - occurs sporadically and in epidemics, with the highest incidence during late winter and early spring -- most epidemics are caused by group A strains, but small outbreaks have occurred with group B and C strains - advanced meningococcal disease can lead to brain damage, coma, and death (fatality rate 9-12% if treated; much higher if untreated 70-80%) - Meningococcal meningitis is now the most common form of meningitis -- since the introduction of Hib (Haemophilus influenza type b) conjugate vaccine, this disease has become the number one killer of children aged 1–5 years |
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Treatment and Prevention of meningococcal meningitis
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- Penicillin = drug of choice
(a) doesn't penetrate normal blood-brain barrier but readily penetrates blood-brain barrier when meninges are acutely inflamed (b) chloramphenicol or a third-generation cephalosporin in persons allergic to penicillins - vaccines directed against group-specific capsular polysaccharides developed [a polyvalent vaccine against groups A, C, Y and W135 can be given to children 2 or older] |
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Eikenella (general characteristics)
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- Eikenella corrodens: part of the gingival and bowel flora in 40-70% of humans
- Gram negative rods or coccobacilli (pleiomorphic = not stuck to one shape) - found in mixed flora infections associated with contamination from normal colonization sites - occurs frequently in infections from human bites - resistant to clindamycin; susceptible to ampicillin and 3rd gen cephalosporins |
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Kingella (general characteristics)
[K. kingae and K. denitrificans] |
- gram-negative rods, but may resemble coccobacilli or diplococci
- part of normal oral flora and occasionally cause infections of bone, joints, and tendons - may enter the circulation with minor oral trauma such as tooth brushing - susceptible to penicillin, ampicillin, and erythromycin |
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Haemophilus (general characteristics)
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- gram-negative coccobacilli
- genus includes a number of species that share a common morphology and a requirement for blood-derived factors during growth that has given the genus its name - H. influenzae is major pathogen in the genus (a) encapsulated or typable strains -- seven types (a through f including e') based on the antigenic structure of capsular polysaccharide (b) unencapsulated or nontypable strains -- type b H. influenzae is by far the most virulent organism in this group -- non-typable strains are frequent causes of respiratory tract disease in infants, children, and adults |
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H. Influenzae type B (general characteristics)
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- until implementation of widespread vaccination programs, was most common cause of meningitis in children between the ages of 6 mo-2 yrs
-- vaccination is w/ type b polysaccharide capsule components - also causes cellulitis and epiglottitis, a condition in which the epiglottitis becomes inflamed and swells, closing off the upper airway - encapsulated organisms can penetrate the epithelium of the nasopharynx and invade blood capillaries directly |
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Nontypable H. influenzae
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- major pathogen that colonizes the human respiratory tract
- respiratory infections include: sinusitis, otitis media, acute tracheobronchitis, and pneumonia - adherence mediated by pili |
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Name three other Haemophilus species (besides H. influenzae) and what they cause
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(1) H. parainfluenzae - pneumonia and endocarditis
(2) H. ducreyi - genital chancre (3) H. aegyptius - conjunctivitis or Brazilian purpuric fever |
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Pseudomonas sp. (general characteristics)
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- gram –, straight or slightly curved bacilli, typically arranged in pairs
- polar flagella - non-fermenting - can grow anaerobically if nitrate or arginine present to act as electron acceptor - cytochrome oxidase - green pigment - β-hemolysis (kills RBC when streaked in blood cell plate) - sweet grapelike odor - VERY UBIQUITOUS - P. aeruginosa is most important species (medically) |
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Pseudomonas sp. (infections, virulence factors, and resistance)
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- Infections in Man (primarily opportunistic)
(a) pulmonary infections CF (b) burn wounds (c) urinary tract infections (UTI’s) (d) external otitis media (“Swimmer’s ear”) (e) eye infection due to contacts (f) can cause bacteremia and endocarditis in compromised individuals - other infections: folliculitis (contaminated hot tubs, pools, spas; acne sufferers and those who depiliate leg hair; fingernail infections in those with hands in water a lot – incl. nail salon patrons) - many strains are resistant to a wide range of antibiotics (Ab resistance: beta-lactamases, porin proteins restricting access of antibiotics) - multiple virulence factors incl: Type 3 SS, exotoxins, LPS, pili, etc. |
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Moraxella (general characteristics) - related to Pseudomonas
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- found on membranes of humans and other warm-blooded animals.
- most species are nonpathogenic - M. lacunata: eyes; conjunctivitis if poor hygiene. - M. nonliquefaciens: upper respiratory tract (esp. nose); may be a secondary invader in respiratory infections - M. urethralis: urine and the female genital tract [can be mistaken for N. gonorrhoeae] - M. catarrhalis: normal flora (nasopharynx) in 40-50% of school children (a) an infrequent, yet significant, cause of severe systemic infections such as pneumonia, meningitis, and endocarditis. (b) an important cause of lower respiratory tract infections in adults with chronic lung disease and a common cause of otitis media, sinusitis, and conjunctivitis in otherwise healthy children and adults |
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Aggregatibacter (Actinobacillus)
- list the main specie - three infections it causes |
- A. actinomycetemcomitans
- Periodontitis, endocarditis, bite wound infections |
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Characteristics of A. actinomycetemcomitans (A.a.)
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- gram-negative, facultative anaerobic coccobacillus
- causes aggressive periodontitis - present in patients w/ chronic periodontitis and periodontally healthy individuals - proportions and serotypes of infected strains in different periodontal conditions are different - causative agent for other serious systemic infections (ex. endocarditis) - can see antenna like protrusions at surface of bacterium (not present in emaA mutant strains but can be restored by transformation) |
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Virulence Factors of A.a
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- unique leukotoxin encoded by IktA gene contributes to killing of human neutrophils and monocytes
- fimbriae (closely associated w/ its ability to colonize various types of host cells) - EmaA (extracellular matrix protein adhesin A) - mediates adhesion to collagen |
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Bordetella
- list three categories of species - what infections do they cause? |
- B. pertussis and B. parapertussis [cause pertussis (whooping cough) in humans]
- B. bronchiseptica [cause respiratory disease in animals and sometimes in humans] - B. avium and B. hinzii [cause respiratory disease in poultry and very rarely found in humans] |
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Characteristics of Bordetella
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- small, Gram-negative, aerobic coccobacilli
- encapsulated and does not produce spores - B. pertussis and B. parapertussis are nonmotile (human pathogens) - B. bronchiseptica are motile (animal pathogens, but can be transmitted to humans) - zoonotic = diseases transferred from animals to humans |
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Characteristics of Pertussis/Whooping cough
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- transmission by droplets; bacteria only colonize ciliated cells of respiratory mucosa
- 1-2 wk incubation period - begins w/ catarrhal phase that lasts 1-2 wks [characterized by low-grade fever, rhinorrhea, and progressive cough; patient is highly infectious] - then comes paroxysmal phase which lasts 2-4 wks [characterized by severe and spasmodic cough episodes] - then is convalescent phase that lasts 1-3 wks [characterized by continuous decline of cough before patient returns to normal] - serious complications, sometimes fatal, are bronchopneumonia and acute encephalopathy |
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Characteristics of Pertussis toxin (a virulent factor of B. pertussis)
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- A-B protein exotoxin: A - catalytic, B - cell receptor binding [B is missile that delivers warhead (A) to destination]
-toxin reacts with different cell types, including T cells, and acts on different cellular regulatory processes - a member of the family of ADP-ribosylating bacterial toxins [ADP-ribosylates Cys352 of protein Gi (GTP-binding protein), as well as the corresponding cysteine of protein Ga and of transducin] - pertussis toxin synthesized solely by B. pertussis but both B. parapertussis and B. bronchiseptica possess genes for pertussis toxin without expressing them [B. parapertussis expresses pertussis toxin when the toxin gene from the B. pertussis chromosome is introduced into B parapertussis] |
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List other virulent factors (besides pertussis toxin) of B. pertussis
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- Filamentous hemagglutinin [causes RBCs to clump]
- Heat-Labile Toxin - Adenylate Cyclase Toxin [screws up cAMP signaling] - Tracheal Cytotoxin [ciliated cells shred] - Lipopolysaccharide - Agglutinogens [14 different ones; some species specific; substances that simulate formation of agglutinin = substances that cause particles to congeal, or form a mass] - heat-labile toxin, adenylate cyclase toxin, tracheal cytotoxin, and LPS formed by three Bordetella species that cause disease in humans, whereas pertussis toxin is produced solely by B. pertussis - B. pertussis organisms undergo antigenic variation to evade immune system |
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Epidemiology of Bordetella Disease
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- mucous membranes of the human respiratory tract are natural habitat for B. pertussis and B. parapertussis
(a) Most infections occur after direct contact with diseased persons specifically, by inhalation of bacteria-bearing droplets expelled in cough spray (b) patient is most infectious during the early catarrhal phase, when clinical symptoms are relatively mild and noncharacteristic - natural habitat of B. bronchiseptica is the respiratory tract of animals such as rabbits, cats, and dogs [human infections extremely rare and occur only after close contact with carrier animals] |
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Treatment and Prevention of B. pertussis
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- B. pertussis is susceptible in vitro to several antibiotics, including tetracycline, erythromycin, and chloramphenicol
(a) erythromycin (Ab of choice) - eliminate viable pertussis organisms from respiratory tract within few days (b) treatment has no influence on course of disease - pertussis vaccine was originally produced from smooth forms (phase I) of the bacteria as a killed whole-cell vaccine - acellular pertussis vaccines were developed, and have been licensed, in Japan since 1981 (a) vaccines were very different and contained structural components from bacteria [like pertussis toxin (which is detoxified) and filamentous hemagglutinin] (b) licensed in the U.S. for booster vaccinations since 1991 (c) recently licensed for primary vaccines in infants |
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Brucella and Francisella
- cause what two diseases? - what bioterrorism agent categories do they belong to? - get from what source? |
- Zoonotic diseases (Brucellosis
& Tularemia) - Brucellosis (Brucella species) is a Category B bioterrorism agent - Tularemia (Francisella tularensis) is a Category A bioterrorism agent - get from animal infections (ex. tick/fly, etc.) |
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Distinguish b/w category A, B, and C of bioterrorism agents
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- Category A: high-priority agents include organisms that pose a risk to national security b/c they
(a) can be easily disseminated or transmitted from person to person (b) result in high mortality rates and have the potential for major public health impact (c) might cause public panic and social disruption (d) require special action for public health preparedness - Category B: second highest priority agents include those that (a) are moderately easy to disseminate (b) result in moderate morbidity rates and low mortality rates (c) require specific enhancements of CDC's diagnostic capacity and enhanced disease surveillance - Category C: third highest priority agents include emerging pathogens that could be engineered for mass dissemination in the future b/c of (a) availability (b) ease of production and dissemination (c) potential for high morbidity and mortality rates and major health impact |
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Characteristics of Brucella
- list three species that are important human pathogens - what is brucellosis? |
- 3 species B. melitensis, B. abortus and B. suis are important human pathogens
- gram-negative coccobacilli; non-spore-forming and non-motile; aerobic, but may need added CO2 - 2 different O chains occur in the LPS of the brucellae w/ smooth colonies [called A and M, nominally indicating abortus and melitensis antigens] - brucellosis is a zoonosis, acquired from handling of infected animals or consuming contaminated milk or milk products (a) severe acute febrile disease caused by bacteria of the genus Brucella (b) exposure if frequently occupational (c) disease now uncommon in U.S. and Britain, but common in Mediterranean and Arabian Gulf regions, Latin America, Africa, and parts of Asia (d) relapses are not uncommon; focal lesions may occur in bones, joints, and other sites; chronic infections may occur |
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Brucellosis
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- symptoms are variable
(a) incubation period difficult to determine (usually 2-4 wks) (b) onset may be insidious or abrupt (c) subclinical infection is common - simplest cases (a) onset is influenza-like with fever; limb and back pains are unusually severe, and sweating and fatigue are marked (b) if the disease is not treated, the symptoms may continue for 2 to 4 weeks - recover spontaneously or suffer series of exacerbations - produce undulant fever (intensity and symptoms recur and recede at ~10 day intervals) - anemia - true relapses may occur months after initial episode, even after apparently successful treatment - most affected persons recover entirely within 3 to 12 months but some will develop complications marked by involvement of various organs, and a few may enter an ill-defined chronic syndrome (a) complications include arthritis, often sacroiliitis, and spondylitis (in about 10% of cases), central nervous system effects including meningitis (in about 5%) (b) in contrast to animals, abortion is not a feature of brucellosis in pregnant women (c) hypersensitivity reactions, which may mimic the symptoms of an infection, may occur in individuals who are exposed to infective material after previous, even subclinical, infection |
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Epidemiology of Brucellosis
- what type of animals? - what's the most important source of brucellosis in humans? |
- reservoirs of brucellosis are various wild, feral and (particularly) domestic animals
- Brucella melitensis in sheep and goats represents, by far, the most important source of brucellosis in humans |
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Treatment and Prevention of Brucellosis
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- patients treated with doxycycline, streptomycin and rifampin for 4-6 wks
- prevented by pasteurizing milk, eradicating infection from herds and flocks, and observing safety precautions (protective clothing and laboratory containment) |
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Francisella
- list two species and what they cause (+ symptoms?) - virulence factors |
- F. tularenis and F. philomiragia
- F. tularenis cause Tularemia = glandular fever, rabbit fever, tick fever or deer fly fever - Tularemia has several different forms including ulcers on the skin or mouth, swollen and painful lymph glands, swollen and painful eyes, sore throat, sudden fever, chills, headaches, diarrhea, muscle aches, joint pain, dry cough and progressive weakness [people can also catch pneumonia and develop chest pain, bloody sputum and can have trouble breathing and even sometimes stop breathing] - very small Gram negative coccobacili, strict aerobe - virulence factors: (a) polysaccharide-rich capsule (antiphagocytic) (b) grows intracellularly , survives inside macrophages [inhibits phagosome-lysosome fusion] (c) resistant to killing in serum |
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What are the three forms of Tularemia?
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- Ulceroglandular [painful papule develops at site of infection which progresses to ulceration]
- Oculoglandular [following infection of eye, painful conjunctivitis develops] - Pneumonic [pneumonitis w/ signs of sepsis; develops rapidly after exposure to infected aerosols; high mortality w/o prompt diagnosis and treatment] - considered category A bioterrorism agent b/c aerosolized [lowest infectious dose needed = 1 bug] |
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Epidemiology of F. tularensis
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- F. tularensis is endemic in U.S.
- specific subtypes are associated w/ geographic regions and species of vector and host |
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Treatment and Prevention of F. tularensis
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- infections are treated w/ Streptomycin (not always available and has toxicity), gentamicin, fluoroquinolones and doxycycline
- F. tularensis strains produce a b-lactmase that is active against penicillins and cephalosporins - prevention: (a) avoidance of the reservoirs of infection like ticks, rabbits, biting insects [organism is present in tick feces - not saliva. Tick feeding must occur for an extended period of time to cause infection] (b) vaccine is available [lessens severity of disease but doesn't prevent it, is not long lasting] |
