Patho final exam: Yersinia Pestis

Yersinia pestis morphology

• gram negative coccobacillus

• Non-motile

• indole and urease negative

• catalase positive

The “safety pin” appearance when yersinia pestis is stained is due to?

Its large central vacule

What are the three forms of the plague?

• bubonic

• septicemic

• pneumonic

Cause of bubonic plague

flea bite, bacteria injected into the blood

Cause of septicemic plague

progression of bubonic plague or from direct contact with plague victims

Cause of pneumonic plague

airborne exposure to the plague

The plague is a

zoonotic infection

What are the three big pandemics?

• plague of Justinian

• the black death

• the 1894 Hong Kong plague

What were the names of the two scientists sent to Hong Kong during the pandemic

• Shibasaburo Kitasato

• Alexandre Yersin

The sylvatic cycle of the plague occurs in

wild rodents

-vector is wild rodent fleas

-reservoir: wild rodetns

The urban life cycle of the plague occurs in

black rat and other domestic rodents

vector: oriental rat flea

The human cycle of the plague occurs when

direct contact is made with reservoirs or bite from a flea

Are rats to blame of the black death?

Maybe not, as modeling has shown that flea/louse transmission was more likely, fleas tend to bite humans when rodent population is low

What three environments is Y. pestis ready to survive in?

• mammal

• flea

• environment

What regulates Y. pestis genes?

temperature

Are all fleas capable of spreading the plague?

No. Common cat flea virtually incapable of transmission while the oriental rat flea is very effective

What is the pathogenesis of Y. pestis in the flea?

• flea bites bacteremia host, ingesting pathogen

• Y. pestis colonizes the proventriculus and midgut

What virulence factors are needed for survival in the flea?

• yersinia murine toxin

• hmsHFRs operon

• Plasminogen activator (Pla)

Yersinia murine toxin (Ymt) is

• protects bacteria from cytotoxic digestion of blood in gut

• deadly in mice but nontoxic to primates and others

hmsHFRS operon does

-makes major components of biofilm matrix

Plasminogen activator (Pla) in the flea does?

Acts as a coagulase, clotting flea throat and aiding in biofilm formation

Pla is capable of acting as both a:

• plasminogen activator and a coagulase

• function dependent of temperature

Why does Y. pestis form a biofilm?

• blocks passage to the midgut

• flea cannot take a full blood meal and keeps biting

• infectious material regurgitated into new host

If full blockage of the flea needed?

No, as biofilm takes weeks to develop and flea dies within days after the bioflm formation. Species that do not develop Y. pestis biofilms can still transmit the plague

How does the flea infect humans?

• by biting and throwing up some of it’s meal

• plague bacilli multiply and travel to lymph nodes

• causes massive hardening/enlargement of lymph notes

What are buboes?

Massive hardening/enlargement of lymph nodes

What happens when Y. pestis moves to the circulatory system?

• systemic disease

• hemorrhage and necrosis of body parts

• characteristic blackened appendages

If Y. pestis gets into the lungs?

• almost always fatal

• can now spread via aerosols

Plague symptoms

• bubonic: enlarged, tender lymph nodes, fever, chills and prostration

• septicemic: fever, chills, prostration, abdominal pain, shock and bleeding into skin and other organs

• pneumonic: fever, chills, cough and difficulty breathing, rapid shock and death if not treated

Primary inhalation lung infection of the plague is:

• rare

• can propagate person-to-person

• usual starts from a patient with bubonic or septicemic that develops into secondary pneumonia from bacteremia spread

• coughing produces airborne droplets that are inhaled by others

When does death usually occur in the plague?

After initial intracellular growth of bacteria in phagocytes

• this is followed by explosive extracellular proliferation of organisms

• resulting in high-grade bacteremia along with inflammation and necrosis in the lymph nodes, spleen and liver

Most Y. pestis virulence factors are?

Plasmid-encoded

pCD1 is

• 70 kbp plasmid

• carries genes for the T3SS

• Includes Yersinia Outer Proteins (YOPs) and V antigen

• Expressed at low concentrations of calcium at 37 C

pPCP1 is

• 9.6 KBP plasmid (tiny)

• encodes Pla

• bacteriocin pesticin

Bacteriocin pesticin kills

Bacteria of the similar species

pMT1 is

• 101 KBP plasmid

• genes for capsule production

• for YMT

How does Y. pestis evade the immune system?

YOPS

The type 3 secretion system in Y. pestis is:

• made of Yersinia secretion proteins (Yscs)

• Yersinia outer membrane protein (YOP)

• low-calcium response (LCR)

Yops are mostly

Injected effectors, YopB and D translocated early and form a portion of pore in membrane of eukarytic cells

LcrV regulates

The opening of the Type 3 secretion channel

YopT and E disrupt?

Rho-family GTPases, deplymerizing actin

YopE acts by?

• turning off rho-family GTPases(actin remodelers)

• mimics natural host cell processes

YopT act by?

Cleaves Rho-family GTPases away from membrane

YopH and M work by

Disrupting signaling

YopH does?

• mimics host regulatory factors

• interacts with p130Cas and focal adhesion kinase (FAK), necessary for actin rearrangements in phagocytosis

YopM does?

Inhibits inflammasome signaling (trigger for the secretion of IL-1b and IL-18)

YopJ and O work by?

Triggering apoptosis

YOPO does?

• Protein kinase

• also triggers macrophage apoptosis

YopJ does?

• acetylates MapK kinases are serines and threonines that are normally phosphorylated during the MAP kinase cascade

• drives apoptosis of macrophages

Yop B and D do?

Together form the tip of the syringe of T3SS

What are four iron acquisition systems that Y. pestis uses?

• Yersiniabactin (siderophore)

• Yfe and Yfu (Iron sequestration system)

• Heme utilization system (Hmu/Hms)

Yersiniabactin is used?

Early in infection

Yfe and Yfu are used?

Later in infection

Y. pestis survives in the mammalian body by:

promoting dissemination early in infection

• producing antiphagocytic surface proteins

  • F1 (capsular antigen fraction 1), forms fibrillar structures of surface of bacterium that prevent phagocytosis

• producing anti-chemotactic protein

  • Pla (protease), prevents chemotaxis of PMNs to site of inoculation

How is the plague treated?

• gentamicin

• streptomycin

• doxycycline or tetracycline

• trimethoprim-sulfamethoxazole

• chloramphenicol

• cephalosporins and other b-lactams

• fluoroquinolones

How is the plague prevented?

• reduce rodent populations

• flea control

Is there an approved vaccine in the us?

No

Is there an approved vaccine in Europe?

Yes, E76 vaccine, attenuated strain