15: Microbes Causing Human Disease I - Yersinia Pestis Flashcards
What are the three main pathogenic species of Yersinia?
Yersina enterocolitica - causes acute or chronic gastrointestinal-enteric infections in humans
Yersinia pseudotuberculosis - causes pseudotuberculosis in birds, rodents and rarely in humans as well causing tuberculosis like symptoms it is localised in tissue necrosis
Yersinia pestis - causes the plague in humans, rodent and other mammals as well as being uniquely transmitted by fleas
What are the three main types of plague?
Bubonic plague
- inflammatory response to proliferation
- lymph nodes become hot, swollen, tender, hemorrhagic
- formation of a very painful bubo
Septicaemic plague
- organism escapes lymph nodes and disseminates via circulation after 3-5 days
- lysis of bacteria by complement activation releases LPS and causes septic shock
Pneumonic plague
- settles in lungs and parasites lung macrophages causing pneumonia
- secondary pneumonic plague is bubonic first
- airborne infection from person to person causes primary pneumonic plague which skips bubonic, is very rapid
What is the enzootic cycle of Y.pestis?
Rat/mouse to flea to rat/mouse
How is Y.pestis transmitted between humans?
Transmission between humans is airborne through coughing when from either secondary pneumonic plague or primary
How is a bubo formed?
A bubo is formed from the inflammatory response to proliferation of Y pestis in the lymph nodes
What significant adaptation of the Y pseudotuberculosis like ancestor most likely led to the evolution of modern Y pestis?
The evolution of flea borne transmission
- y pseudotuberculosis is not transmitted by fleas and is actually orally toxic to them. Gene loss/mutation has resulted in loss of toxicity in y pestis (loss of urease activity)
- in y pseudotuberculosis urease converts urea to ammonia and cause fleas to get sick. Y pestis has mutation that stops the production of ammonia and prevents fleas from getting sick, which allows colonisation of flea midgut by y pestis
- plasmid pFra encodes a phospholipase required for survival in the flea midgut Y pestis biofilm formation revolved to become activated in the flea, causing blockage and regurgitation
What flea associated phenotype has y pestis lost that facilitates its long term infection of the flea?
Loss of urease activity. In Y. pseudo, urease converts urea to ammonia and causes fleas to get sick. Y. pestis has mutation that stops them producing ammonia and fleas don’t get sick, allowing long term colonisation.
Aside from gene loss and gene acquisition, what other modifications to the Y. pestis genome have likely contributed to its ability to persist in the flea gut?
- Y. pestis and Y. pseudo have the hms locus that’s involved in PNAG production and is required for efficient colonisation of flea and transmission to animals.
- Y. pestis has mutation that makes biofilm formation possible at 28C or less only.
Biofilm formation, blockage of proventriculus and efficient transmission are all
dependent on the Hms locus and PNAG. Y. pseudo does not cause biofilms in flea despite carrying all the same genes as Y. pestis, suggesting that evolved gene regulation is as important as acquisition or loss of gene funtions.
pFra and pPst are unique to Y. pestis, what is known about their contribution to Y. pestis virulence/pathogenesis?
pFra encodes the Yersinia murein toxin, a phospholipase required for cell wall integrity in the flea midgut. pPst encodes the Pla “Plasminogen activator protease”, a serine protease attached to the outside of Y. pestis, required for bubonic and pneumonic forms of plague.
- > Targets numerous mammalian proteins for destruction.
- > Degrades blood clots to facilitate systemic infections, targets proteins involved in
coagulation and fibrinolysis, complement, cationic peptides
What ensures that the type III secretion system is not switched on in fleas?
- Plasmid pYv encodes Ysc, a type III secretion apparatus which is only active at 37C and in a nutrient rich environment
- > flea body temp is typically lower than 28C
Give an example of a Yop protein and its role in infection
- originally described as Yersinia outer membrane proteins
- yopE disrupts actin filaments by inhibiting Rho GTPase
- Prevents formation of phagocytic structures by the target cell
