Lecture 8: Y. PESTIS Flashcards
What is Y. Pestis?
Class A infectious agent with potential for use as a biowarfare or bioterrorism agent
Facultative anaerobe Gram-negative bacillus
uses intracellular type II secretion
What is a plague?
a reemerging disease; reappearance of outbreaks in various countries after decades of quiescence
What are the means of infection of Y. Pestis?
- Y. pestis
- Y. enterocolitica - causes watery diarrhea
- Y. pseudotuberculosis - Disease in animals
What is the path of infection of Y. Pestis?
After ingestion, the bacteria invade the intestinal epithelium by invasion of M cells.
- released at the basal surface.
- penetrate into the underlying lymphoid tissue, where they multiply both inside and outside host cells.
What are the main routes of transmission of Y. Pestis?
- Flea bite
- Direct animal contact
- Contact with tissues, body fluids
- Scratches, bites - Aerosol
What is the mechanism of transmission of Flea bite?
- Organisms ingested during a blood meal from the bacteremic host (e.g., infected rat)
- Bacteria multiply causing blockage of proventriculus (throat parts of flea)
- Flea regurgitates infectious material into new host during subsequent attempts at blood meal
- Flea remains hungry & feeds more aggressively
What is the forest cycle of transmission?
−Y. pestis is maintained in the environment by spread of the organism among rodents
−There is low risk of transmission to humans
What is the urban cycle of transmission?
−The rodent is domestic
−Plague spreads rapidly among susceptible rodents, causing them to die off rapidly
− Their fleas search for new hosts, increasing risk of spread of infection to humans.
What are the 3 major forms of plaque?
- Pneumonic: Inhalation (primary)
- Mortality 57% (>90% if treatment delayed)
- Most likely route for bioterrorism - Bubonic: Flea bite or animal handling
- Mortality <5% (40-60% untreated) - Septicemic - Sepsis
- Mortality 30-50% (>90% untreated)
What are the symptoms of the pneumonic plague.?
Coughing (often coughing blood)
First signs of illness are fever, headache, weakness, and rapidly developing pneumonia with shortness of breath, chest pain, cough
May cause respiratory failure and shock
What are symptoms of the bubonic plague?
- A usual incubation period of 2–6 days
- Constitutional symptoms (i.e, can affect many different systems of the body and are generally unspecific; can cause them to manifest:
chills; fever; headache; weakness) - Swelling of lymph nodes, called a “bubo”
What are the clinical test used to diagnose Y. Pestis?
- An anti-F1 antibody test of serum can differentiate between different species of Yersinia
- Polymerase chain reaction (PCR) can be used to identify Y. pestis.
- Plague diagnostic phages φA1122 and L-413C
What are the 3 plasmids of Y. pestis?
- pYV (pCD1): calcium dependence
- pPla (pPCP1): pesticin, coagulase, plasminogen activator
- pFra (pMT1): murine toxin
Describe the plague vaccine formalin-killed U.S.P.
The killed vaccine did not protect against respiratory exposures, and required multiple doses over time. Also, it could cause severe inflammation
What vaccines for Y. pestis is promising?
At present, recombinant subunit vaccine that expresses both F1 and V antigens of Y. pestis shows promise
What are the treatments for Y. Pestis?
- Supportive care
- Antibiotics
- Aminoglycosides
- Doxycycline, tetracycline, chloramphenicol
What antibiotics are not effective treatments?
-Penicillins and cephalosporins are NOT effective
what is Sepsis?
a whole-body inflammatory response that is caused by severe infection and can be fatal
how are the biovars of Y. pestis differentiated?
through their ability to reduce nitrate and to ferment glycerol and arabinose
how is Y. pestis different from Y. enterocolitica and Y. pseudotuberculosis?
Y. pestis is non motile while the other two are non motile at 37 degrees C and motile at 22 degrees C
how is Y. pestis identified?
- non motile
- bipolar staining
- slow growth of small colonies on ordinary culture media
which virulence plasmid is in all 3 strains of yersinia?
pYV
which plasmids are just in Y. pestis and not the other two?
pFra and pPla
Why are Y. enterocolitica and Y. pseudotuberculosis clinically significant?
- both are acquired by ingestion of contaminated food and water
- both cause a disease involving fever and abdominal pain
- after ingestion, the bacteria invade the intestinal epithelium by invasion of M cells
what type of strains of Y. pestis have been isolated from patients with bubonic plague?
multiple drug resistant strains
what is the reservoir for bubonic plague
infected wild rodents
what are the three forms of plague?
- pneumonic
- bubonic
- septicemic
what are some traits of HPI?
present in all 3 strains of Yersinia, role in high pathogenicity
what are the virulence factors of Y. pestis?
- endotoxin
- murine toxin
- fraction 1
- V antigen
- pPla
- Psa
- iron acquisition and sequestering system
- Yad A
what symptoms is endotoxin responsible for?
hypotension, DIC, and endotoxic shock
what does pFra/murine toxin do?
causes edema and necrosis in mice but not in humans
what is fraction 1?
a protein component of the antiphagocytic protein capsule
What plasmids are unique to Y. Pestis only?
-pPCP1 and pMT1 y
What is Yad A?
an outer membrane protein that interferes with C3b binding to bacteria, thus preventing the formation of a membrane attack complex
– Inactive in Y. pesti
What is Psa (pPla)?
a pilus adhesion for attachments that is specific for Y. pestis, and plays a role in transmission and virulence
What is Pla?
a protease that activates plasminogen activator (acts as a fibrinolysin) and degrades C3b
What does C3b do?
prevents formation of complement membrane attack complex
What is the role of C5a?
prevents attraction of phagocytes
What is pYV/V antigen?
a secreted protein that controls expression of many of the virulence genes plus it appears to have another unknown function that is essential for virulence
what symptoms is endotoxin responsible for?
hypotension, DIC, and endotoxic shock
what does degrading C3Bb and C5a from Pla do?
degrading C3Bb prevents formation of complement membrane attack complex and degrading C5a prevents attraction of phagocytes
What are the 3 biovars of Y. pestis?
- Antigua
- Medievalis
- Orientalis
What is Y. Pestis Bipolar staining?
Wright’s stain (mixture of eosin (red) and methylene blue dyes)
What are symptoms of the septicemic plague?
- Same flu-like illness progressing to sepsis
- No discernible enlargement of the lymphatic glands
- gastrointestinal symptoms of nausea, vomiting, diarrhea, and abdominal pain.
- Necrosis of skin and mucous membranes result in the appearance of dark purplish/ black skin lesions; may be the origin of the term “Black Death”
