Cornyebacteria, Listeria, Bacillus Flashcards
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Q
Cornyebacteriae genus
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2
Q
C. diphtheriae disease: Diphtheria
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Q
C. diphtheriae Toxin
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- Diphtheria toxin blocks host cell protein synthesis, resulting in cell death
- Toxin encoded by a lysogenic bacteriophage
- Toxin can disseminate systemically leading to heart failure, loss of motor control (inability to swallow)
- Effective vaccine – diphtheria toxoid
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Q
C. diphtheriae Toxin MOA
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- Extremely potent: LD is ~100ng/kg body weight
- Extremely versatile: “B” domain can be used as “cargo carrier” (fuse to other molecules, and deliver them into host cell)
5
Q
C. diphtheriae Acute Pharyngitis
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•Clinical presentation: bacterial multiplication in the pharynx leading to pseudomembrane formation:
– The pseudomembrane is due to the combined effects of bacterial growth, toxin production, tissue necrosis and the host immune response
•Swollen neck/throat (“bull neck”); brassy or “barking” cough, stridor, hoarseness, difficulty breathing; pseudomembranes
6
Q
C. diphtheriae Cutaneous Diphtheria
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•Classic cutaneous diphtheria: non-progressive infection with a scaly rash or ulcers with a grey-brown membrane
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Q
C. diphtheriae Diagnosis
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• Throat culture: Growth on selective “Tinsdale” medium
– Gram’s stain + Albert’s stain
8
Q
C. diphtheriae Treatment
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Treatment of diphtheria is directed at neutralization of the toxin with concurrent elimination of the organism.
- Diphtheria antitoxin neutralizes free toxin but has no effect on toxin already bound to cells.
- C. diphtheriae is susceptible to a variety of antimicrobial agents, of which erythromycin has been the most effective.
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Q
C. diphtheriae Prevention
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The mainstay of diphtheria prevention is immunization.
- Three to four doses of diphtheria toxoid (formalin-inactivated DT) produce immunity by stimulating antitoxin production.
- The initial series is begun in the first year of life.
- Booster immunizations at 10-year intervals will maintain immunity.
10
Q
Listeriae genus
A
11
Q
Listeriae species
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• The two pathogenic species are strongly hemolytic due to a similar pore-forming toxin
– Listeriolysin O – L. monocytogenes
– Ivanolysin O – L. ivanovii
• The toxin is a primary virulence factor and non-hemolytic mutants are avirulent
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Q
L. monocytogenes: Human Listeriosis
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13
Q
L. monocytogenes: Listeriosis Epidemiology
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- Members of Listeria are widespread among animals in nature, including those associated with our food supply (fowl, ungulates). The human reservoir appears to be intestinal colonization by ingestion of foods contaminated with animal Listeria.
- Dairy product outbreaks have been traced to consumption of unpasteurized dairy products or postpasteurization contamination.
- A feature of some epidemics has been the ability of L. monocytogenes to grow at refrigerator temperatures (psychrophilic).
- Food prepared from animal products in a ready-to-eat form such as salami are at particular risk of listerial contamination.
- L. monocytogenes may also be transmitted transplacentally to the fetus presumably following hematogenous dissemination in the mother.
- It may also be transmitted to newborns in the birth canal in a manner similar to group B streptococci.
14
Q
L. monocytogenes: Listeriosis Pathogenesis
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- L. monocytogenes follows a stepwise invasive process which is very similar to the Gram negative rod Shigella.
- The major steps for Listeria are:
- Various surface proteins mediate attachment to fibronectin that is surface-displayed by enterocytes (intestinal epithelial cells).
- Bacterial internalin attaches to a host receptor (E-cadherin), which stimulates reorganization of the host cell’s cytoskeleton and facilitates bacterial entry within a membrane-bound vacuole.
- The invading bacteria escape into the host cell cytoplasm through the action of listeriolyson O (LLO) which lyses the vacuolar membrane.
- In the cytosol, the bacteria move through the cell by controlling the metabolism of the cell’s actin filaments.
- The cell’s actin skeleton and microtubule infrastructure are disrupted.
- Listeria reaching the edge of the cell protrude into an adjacent cell and infect it as well.
- This allows lateral spread from epithelial cell to epithelial cell without exposure to the immune system.
- New research reveals that L. monocytogenes has a protein PrfA that is a thermosensor. PrfA control the expression of listeria virulence genes only at 37°C (and not lower temperatures); thus, toxic proteins are efficiently synthesized only when the pathogen is inside the host.
15
Q
L. monocytogenes: Listeriosis Manifestations
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- Older adults: sepsis or meningitis; sometimes focal infection (septic arthritis)
- Infants: Early-onset (<6d post-birth);trans-placental
- Pregnant women: flu-like
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Q
L. monocytogenes: Listeriosis Diagnosis
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•Culture (usually blood, placenta, CSF)
17
Q
L. monocytogenes: Listeriosis Treatment
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•Antibiotics; severe cases IV ampicillin or gentamycin; CDC does not recommend stool testing
18
Q
Bacillus genus
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- The genus Bacillus includes many species of aerobic or facultative, spore-forming, Grampositive rods.
- With the exception of one species, B. anthracis, they are low-virulence saprophytes widespread in air, soil, water, dust, and animal products.
- B. anthracis causes the zoonosis anthrax, a disease of animals that is occasionally transmitted to humans.
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Q
B. anthracis
A
- A polypeptide (poly-d-glutamic acid) capsule has antiphagocytic properties.
- Produces a three-protein exotoxin composed of the molecules edema factor (EF), lethal factor (LF) and protective antigen (PA). PA+LF is lethal; PA+EF produces edema; EF+LF has no activity, and PA+EF+LF is lethal.
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Q
B. anthracis Epidemiology
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- Anthrax is primarily a disease of herbivores such as horses, sheep, and cattle who acquire it from spores of B. anthracis contaminating their pastures.
- Humans become infected through contact with these animals or their products in a way which allows the spores to be inoculated through the skin or inhaled.
- The rare naturally-occurring case today is virtually always traceable to animal products such as wool, hides, or bone meal fertilizer which have been imported from a country where animal anthrax is endemic.
- The real threat of anthrax comes from its continuing appeal to those bent on using it as an agent of biologic warfare or terrorism. The long life, stability, and low mass of the dried spores make the prospect of someone producing a “cloud of death” leading to massive pulmonary anthrax a worldwide concern.
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Q
B. anthracis Pathogenesis
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- When spores of B. anthracis reach the rich environment of human tissues they germinate and multiply in the vegetative state.
- The antiphagocytic properties of the capsule aid in survival, eventually allowing production of large enough amounts of the exotoxin complex to cause disease.
- Importantly, combinations of Rapid progression to bacteremia is common.
22
Q
B. anthracis Manifestations: Cutaneous Anthrax
A
- Cutaneous anthrax usually begins 2 to 5 days after inoculation of spores into an exposed part of the body, typically the forearm or hand.
- The initial lesion is an erythematous papule, which may be mistaken for an insect bite.
- This papule progresses through vesicular and ulcerative stages over 7 to 10 days to form a black eschar (scab) surrounded by edema. This complex is known as the “malignant pustule.
- Associated systemic symptoms are usually mild, and the lesion typically heals after the eschar separates.
23
Q
B. anthracis Manifestations: Pulmonary Anthrax
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- Pulmonary anthrax is the form we would expect from the dissemination of a spore aerosol in biologic warfare.
- After 1 to 5 days of nonspecific malaise, mild fever, and nonproductive cough, progressive respiratory distress and cyanosis
- There is massive edema of the neck, chest, and mediastinum.
- If untreated, progression to a fatal outcome is usually very rapid once edema and bacteremia have developed.
24
Q
B. anthracis Manifestations: Gastrointestinal Anthrax
A
- Rare form of anthrax infection in humans
- Spores enter gut through ingestion of contaminated under-cooked meat
- Extensive gut damage (necrosis, hemorrhage)
- Case fatality rate: 25-60% without antibiotic treatment
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B. anthracis Diagnosis
* The primary diagnostic method is culture of B. anthracis from skin, sputum or blood.
* The organism requires no special media for isolation but separation of B. anthracis from the much more common saprophytic Bacillus species requires methods and experience present in few clinical laboratories.
* Notifying the laboratory of the suspicion of anthrax is important to prevent the pathogen from being discarded as a contaminant.
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B. anthracis Treatment
* Antimicrobial treatment has little effect on the course of cutaneous anthrax but does protect against dissemination.
* Almost all strains of B. anthracis are susceptible to penicillin which has long been the treatment of choice for severe forms of anthrax.
* Doxycycline or ciprofloxacin are alternatives and are also recommended for chemoprophylaxis in the case of known or suspected exposures
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B. anthracis Prevention
* The most important preventive measures are those which eradicate animal anthrax and limit imports from endemic areas.
* The vaccine used by the United States military is prepared from filtrates of a nonencapsulated B. anthracis strain which produces a component of the toxin complex.
* Vaccine acceptance is complicated by fears that the architects of biologic warfare may have crafted strains for which this vaccine is not protective.
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Other Bacillus Species
* Bacillus spores are widespread in the environment, and isolation of one of the more than 20 Bacillus species other than B anthracis from clinical material usually represents contamination of the specimen.
* Occasionally B. cereus, B. subtilis, and some other species produce genuine infections, including infections of the eye, soft tissues, and lung.
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B. cereus
* B. cereus deserves special mention. This species is the one most likely to cause opportunistic infection, which suggests a virulence intermediate between that of B. anthracis and the other species.
* Genes and plasmids similar to those found in B. anthracis have been detected as has a destructive pyogenic toxin. B. cereus can also cause food poisoning by means of enterotoxin production.
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