Shigella

transmission of shigella

fecal-oral (poor hygeine and incontinence) and direct person-person contact

transmission of shigella in LMICs

commonly through contaminated food or water

What are the four serogroups of shigella

1. Shigella dysenteriae

2. Shigella flexneri

3. Shigella boydii

4. Shigella sonnei

What is the most common cause of diarrhea among the serogroups

S. flexneri

Among the serovars of shigella, what are the least comon causes of diarrhea

S. boydii and S. dysenteriae

Impact of the S. dysenteriae serogroup

high mortality rate and causes outbreaks in war-torn countries

what is the most common cause of shigella infections in high-income countries?

S. sonnei

Which shigella serotypes cause dysentery

S. flexneri and S. dysenteriae

What are typical shigella infections characterized by?

acute inflammatory colitis and bloody diarrhea

typical length of a shigella infection in an otherwise healthy individual

5-7 days; self-limiting

shigella in immunocompromised people or the extremes of age

• can be prolonged

• can lead to bacteremia which causes a lot of mortality in malnourished kids

• HUS

• colonic perforation

• intestinal obstruction

• toxic megacolon

HUS

hemolytic uremic syndrome

Why is the shigella infectious dose so low compared to other organisms?

acid tolerant so they are able to get by the stomach to the small intestine/large intestine with a low infectious dose

How does shigella survive a very acidic environment

GadAB and AtpAD combine to control proton flow and fine tune intracellular pH

• GadAB: glutamate decarboxylase system

• AtpAD: ATP synthase that can work in reverse and pump protons out

When does shigella start making toxins

once it gets past the stomach

ShET1 is primarily produced by which serogroup?

S. flexneri

function and structure of ShET1

• Fe-dependent AB toxin encoded on the chromosome

• responsible for the early phase of diarrhea

Which species produce SHET 2

almost all; encoded on different genes on plasmids

function of SHET2

early phase of diarrhea

Which shigella strains produce the shiga toxin

dysenteric strains

Stages of Shiga-toxin action

1. B5 homopolymer binds receptor enriched on intestinal and kidney cells

2. retrograde traffic to ER

3. disulfide is released in ER and A1 is released

4. A1 deactivates 28S rRNA and inhibitis protein synthesis

5. apoptosis and necrosis of cells

What is the shiga toxin responsible for?

HUS and hemorrhagic colitis

What does Shigella use to invade

• T3SS (encoded by the mxi-spa locus on a plasmid) translocates IcsA to host cells to facilitate initial N-WASP association

• IpaD blocks pore until cholesterol and sphigomyelin are sensed and tell the bact that the host cell is nearby

• IpaB and IpaC are recruited and form pore into host cell

• IpaBCD are released and bind integrin to mediate actin rearrangement

When does the Shigella T3SS get reactivated?

when cell-to-cell spread is needed

How does Shigella accomplish cell-to-cell spread

• T3SS reactivates and translocates IcsA into the host cell cytoplasm that the bacteria is within

• IcsA attaches to the old pole of the cell and mimics Cdc42

• N-WASP is recruited → Arp2/3 is recruited

• a synthetic actin polymerization complex forms on the old pole that leads to the production of actin tails → bacteria is propelled into adjacent cells

how is shigella treated

supportive care with hydration and electrolyte management; in some cases antibiotics are used

when are shigella antibiotics used

• fluoroquinolones, azithromyocin, and cephalosporins are used if risk of resistance is low

• carbapenems are used if resistance is possible

• AMR is increasing

how does shigella get out of the phagosome

Starts with IpgD:

• IpgD becomes PIP2 and PIP5

• PiP5 leads to TOM1 recruitment —> inhibitiiton of endosomal recruitment

• PIP5 promotes actin rearrangement to induce more invasion

• PIP5 activates Akt to promote cell survival

• PIP5 promotes recruitment of Rab11 to the point it leads to vaculole repture