Shigella and E coli

Question 1

What are all of the “enteric” bacteria?

Answer 1

• Shigella
• E coli
• Salmonella
• Vibrio
• Campylobacter
• Helicobacter
• Y enterocolitica and pseudotuberculosis
• Pseudomonas
• Bacteroides/Prevotella
• Clostridium
• Klebsiella/Enterobacter/Serratia
• Proteus/Providencia/Morgenella
• Listeria (only gram positive!)

Question 2

What is the bacteriology of Shigella?

Answer 2

• gram neg rods
• NOT lactose fermenting -MacConkey medium
• Not H2S producing
• Non-motile
• facultative anaerobe
• facultative intracellular

Question 3

What is a Shigella infection?

Answer 3

• Shigella enterocolitis= bacillary dysentery= shigellosis
• very low infectious dose (~100 IUs)
• bloody diarrhea, local inflammation, ulceration
• mortality risk less than 1% in developed countries but fatality can reach 30% in developing countries/ malnutrition status
• risk of reactive arthritis-children under 5 at highest risk for infection both in US and abroad (also HIV+, MSM) though breast milk appears to be protective for 0-6 month babies

Question 4

What is Reactive arthritis?

Answer 4

• Reiter’s Syndrome
• autoimmune sequelae of bacterial infection in patients with HLA-B27
• conjunctivitis + urethritis +arthritis
• can’t see, can’t pee, can’t climb a tree
• treated with NSAIDs

Question 5

What is the pathogenesis of Shigella infection?

Answer 5

• shigella invades epithelium of distal ileum and colon epithelium (via M cells, then infects macrophages) and secrete exotoxins
• exotoxin pathway kills adjacent cells (goes backwards and sideways)
• local infection->cell necrosis, apoptosis, host inflammatory response and hemorrhage lead to bloody diarrhea

Question 6

What are the virulence factors of Shigella?

Answer 6

• virulence depends on 220KB plasmid- Shigella that lose it not virulent, E coli that gain it (O157:H7) are
• protein-synthesis-inhibiting shiga toxin (Stx) is plasmid-encoded. Other toxins are chromosome-encoded but don’t so dramatically determine virulence
• plasmid also carries genes for siderophores (Shu, aerobactin), iron-chelating molecules that allow the bacteria to parasitize enough iron to grow to large numbers
• entry of Shigella mediated by type III secretory system and other effector proteins and cytoskeletal rearrangements-
• IcsA- actin based motility, bacterial use of host actin to cross into neighboring cells directly
• IpaB- induces macrophage apoptosis-> no phagocytosis that would increase inflammatory response

Question 7

What do M cells do?

Answer 7

• they are in the Peyer’s patch of intestines

- they preform immunological testing

Question 8

What is HUS?

Answer 8

• hemolytic uremic syndrome begins when shiga toxin escapes into bloodstream
• sets off a immunological/hematological cascade leading to acute hemolysis, renal failure, uremia, and DIC
• mortality rate about 10%

Question 9

How does Shigella look on physical exam?

Answer 9

• fever, dehydration, severe headache, lethargy, diarrhea progresses from watery to bloody with mucus
• HUS- fever, dehydration, hemolysis, thrombocytopenia, uremia requiring dialysis
• very young and old most severely affected

Question 10

How does Shigella look on labs?

Answer 10

• strain determined by lab immunoassays (agglutination)
• methylene blue stain of fecal sample reveals whether neutrophils are present (Shigella, Salmonella, Campylobacter) or not (V. cholerae, E. coli, C. perfringens)

Question 11

How does HUS look on labs?

Answer 11

-bloodwork for: schistocytes, decreased platelets, increased PMNs, increased lactate dehydrogenase

Question 12

What is the treatment and prevention of Shigella?

Answer 12

• fluid and electrolyte replacement
• full blown cases: culture organism and test for Ab sensitivity; ceftriaxone, fluoquinolone, azithromycin, or cefixime usually work in adults- no fluoroquinolone for children
• in Shigella, Ab treatment decreases HUS risk (opposite EHEC)
• NO ANTIDIARRHEAL MEDS
• if malnourishment is possible, supplement vit A and zinc
• prevention by sewage disposal, water chlorination, handwashing

Question 13

What is the bacteriology of E. coli?

Answer 13

• straight gram neg rod
• facultative anaerobe
• Lactose fermenter- pink on MacConkey plate
• H2S negative, urease negative
• may be mobile (flagella) or nonmobile
• normal GI fauna

Question 14

What pathology can E coli cause?

Answer 14

• enterotoxigenic diarrhea
• enterohemorrhagic diarrhea
• UTIs
• Meningitis
• Pneumonia
• Intra-abdominal escape after GI perforation

Question 15

What are the different types of enteropathogenic E coli?

Answer 15

• *ETEC
• EPEC
• EIEC
• EHEC
• EAggEC
• EAEC

Question 16

What is Enterotoxigenic E coli (ETEC)?

Answer 16

• fimbriae for adherence to host cell, enterotoxin delivery; travelers diarrhea; small bowel

Question 17

What is Enteropathogenic E coli (EPEC)?

Answer 17

• Intimin/Tir complex type 3 or 4 secretion system inject molecules to force cell to form actin bundle causes inflammation; childhood diarrhea; small bowel

Question 18

What is Enteroinvasive E coli (EIEC)?

Answer 18

• intracellular just like Shigella entry; Shigella-like dysentery; large bowel

Question 19

What is Enterohemorrhagic E coli (EHEC)?

Answer 19

Shiga toxin delivery via T3SS; is infected by phage STX, produces Shiga toxin, causes hemorrhagic colitis or HUS; large bowel

Question 20

What is Enteroaggregative E coli (EAggEC)

Answer 20

• associated with persistent diarrhea in children in developing countries; small bowel

Question 21

What is enteroadherent E coli (EAEC)

Answer 21

• childhood diarrhea nad traveler’s diarrhea in Mexico and North Africa; small bowel

Question 22

What is the pathogenesis of enterotoxigenic diarrhea?

Answer 22

• pili attach to jejunum and ileum
• enterotoxins (heat-liable or stable synthesized)
• enterotoxin LT forces host membrane-bound ion transporters to expoirt
• host loses fluid, potassium and chloride
• watery diarrhea

Question 23

What is the pathogenesis of enterohemorrhagic diarrhea?

Answer 23

• EHEC attach to the mucosal epithelial cells of the colon; may invade
• lysogenic phage STX encodes Shiga toxin (1 or 2)
• shiga toxin becomes active inside gut cells, shuts down protein synthesis, destroys some
• inflammation
• bloody diarrhea
• toxin may reach bloodstream-> risk of HUS: 9-30% proceed to this, associated with use of antibiotics to treat bloody diarrhea

Question 24

What does the Shiga toxin do in the blood?

Answer 24

• cytokine disregulation- inc PMNs, inc TNFalpha, inc IL1, inc IL6, inc vWF
• capillary occlusion-fibrin-plately thrombi in renal microvasculature
• kidney failure- lactate dehydrogenase-> hemolytic anemia
• Gb3 receptor -> CNS involvement
• accessory virulence factors
• nephrotoxicity
• host factors? full recovery 60%, major sequelae 30%, DIC 10%

Question 25

How is E coli diagnosed?

Answer 25

- bloody or nonbloody diarrhea, dehydration, recent travel abroad - culture stool sample on blood agar and differential medium (MacConkey), EIA test colonies for Shiga toxin. - HUS on labs

Question 26

How do you treat E coli?

Answer 26

- enterotoxic diarrhea- self-limited, rehydrate - enterohemorrhagic diarrhea- no antimotility agents, antibiotics associated with increased HUS risk (opposite of Shigella), just rehydration - HUS- dialysis, IV hydration, treat hypertension, new antitoxin treatment research

Question 27

Non-infectious bacterial-toxigenic gastroeneteritis

Answer 27

- S aureus food poisoning, Bacillus cerus food poisoning, and Foodborne botulism - neuro- and/or entero-toxins are secreted by bacteria growing on food - patient consumes food - bacteria lack GI virulence factors and do not survive ingestion to cause an infectious process but the preformed toxin cause disease - caused by B cereus enterotoxins, C botulinum neurotoxin, S aureus-both - fast onset- hours not days - provide supportive care, particularly rehydration, botulism may need more treatment - trace outbreak by testing leftovers