Cornyebacteria, Listeria, Bacillus Flashcards
Cornyebacteriae genus
C. diphtheriae disease: Diphtheria
C. diphtheriae Toxin
- 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
C. diphtheriae Toxin MOA
- 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)
C. diphtheriae Acute Pharyngitis
•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
C. diphtheriae Cutaneous Diphtheria
•Classic cutaneous diphtheria: non-progressive infection with a scaly rash or ulcers with a grey-brown membrane
C. diphtheriae Diagnosis
• Throat culture: Growth on selective “Tinsdale” medium
– Gram’s stain + Albert’s stain
C. diphtheriae Treatment
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.
C. diphtheriae Prevention
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.
Listeriae genus
Listeriae species
• 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
L. monocytogenes: Human Listeriosis
L. monocytogenes: Listeriosis Epidemiology
- 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.
L. monocytogenes: Listeriosis Pathogenesis
- 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.
L. monocytogenes: Listeriosis Manifestations
- Older adults: sepsis or meningitis; sometimes focal infection (septic arthritis)
- Infants: Early-onset (<6d post-birth);trans-placental
- Pregnant women: flu-like
B. anthracis
- 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.
B. anthracis Manifestations: Cutaneous Anthrax
- 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.
B. anthracis Manifestations: Pulmonary Anthrax
- 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.
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.
