Escherichia

Question 1

Disease

Answer 1

• UTI & gram-negative rod sepsis
• neonatal meningitis and the agent
• traveler’s diarrhea
• Some strains -> enterohemorrhagic-> bloody diarrhea.

Question 2

Important Properties

Answer 2

• straight gram-negative rod
• most abundant facultative anaerobe
  in colon & feces; outnumbered
  by obligate anaerobes (Bacteroides).
• ferments lactose, has 3 antigens-> various combinations result in
  more than 1000 antigenic types of E. coli.
• O55 and
  O111 cause outbreaks of neonatal diarrhea).

Question 3

Pathogenesis

Answer 3

• Reservoir : humans & animals.
• UTI Source: colonic flora that colonizes urogenital area.
• Neonatal meningitis Source: mother’s birth canal; infection acquired during during birth.
• Traveler’s diarrhea Source: ingestion of food or water contaminated with human feces.
• Main reservoir of enterohemorrhagic E. coli O157 is cattle & organism acquired in undercooked beef (hamburgers).
• components that cause disease: pili, capsule, endotoxin, & 3 exotoxins (enterotoxins), 2 cause watery diarrhea and 1 bloody diarrhea & hemolytic–uremic syndrome.

Question 4

Intestinal Tract Infection

Answer 4

• 1st step-> adherence to jejunum & ileum cells by pili protruding from bacterial surface.
• 2nd step->bacteria
  synthesize enterotoxins, act on jejunum & ileum cells & cause diarrhea.
• Toxins cell-specific; colon cells not susceptible-> lack receptors for the toxin.
• Enterotoxigenic strains
  of E. coli (ETEC) produce
  2 enterotoxins.
  (1) Heat-labile toxin (LT)
  (2) Heat-stable toxin (ST)

Question 5

Intestinal Tract Infection: (1) Heat-labile toxin (LT)

Answer 5

• Stimulates adenylate
  cyclase.
• catalyses ADP-ribosylation to G protein irreversibly activating cyclase-> increase in intracellular cyclic AMP stimulating cyclic AMP–
  dependent protein kinase
  -> phosphorylates ion
  transporters in membrane.
• Transporters export
  ions-> outpouring of fluid, K & Cl from enterocytes into lumen of gut-> watery diarrhea.
• cholera toxin same mode of action.

Question 6

Intestinal Tract Infection: (2) Heat-stable toxin (ST)

Answer 6

• low-molecular-weight
• Stimulates guanylate cyclase.
• Enterotoxin-producing strains don’t cause inflammation, don’t invade intestinal mucosa, & cause watery, nonbloody diarrhea.
• Enteropathic strains (enteroinvasive) cause disease not by enterotoxin formation but by invasion of large intestine epithelium causing bloody diarrhea (dysentery)
  accompanied by inflammatory cells (neutrophils) in stool.
• Enterohemorrhagic (EHEC) strains(O157:H7 serotype) (STEC) cause bloody diarrhea by producing exotoxin Shiga toxin (similar to Shigella speciestoxin).
• Removes adenine from
  large (28S) rRNA stopping protein synthesis.
• encoded by temperate (lysogenic) bacteriophages. - Also called verotoxin-> cytopathic effect on Vero (monkey) cells in culture.

Question 7

Intestinal Tract Infection: Hemolytic–uremic syndrome (HUS)

Answer 7

• Shiga toxin enters bloodstream.
• hemolytic anemia, thrombocytopenia, & acute renal failure,
• Receptors for Shiga toxin on endothelium surface of small blood vessels & kidney epithelium surface. - Death of endothelial cells of small blood vessels-> microangiopathic hemolytic anemia-> red cells passing through damaged area become grossly distorted (schistocytes) & then lyse.
• Thrombocytopenia occurs because platelets adhere to damaged endothelial surface.
• Death of kidney epithelial
  cells -> renal failure.
• Treatment of diarrhea by
  O157:H7 strains with ciprofloxacin increases the risk of developing HUS by increasing Shiga toxin amount released by dying bacteria.

Question 8

UTIs

Answer 8

• uropathic strains
• pili with adhesin proteins bind to specific receptors on urinary tract epithelium.
• Binding site on receptors consists of dimers of galactose (Gal-Gal dimers).
• Pili/P fimbria/ pyelonephritisassociated
  pili (PAP).
• Cranberry juice contains flavonoids inhibit pili
  binding to receptors
• prevents recurrent UTIs.
• E. coli Motility->ascend urethra into bladder & kidney.

Question 9

Systemic Infection

Answer 9

2 structural components

(1) Polysaccharide Capsule
- interferes with phagocytosis-> enhances ability to cause infections in various organs.
- Neonatal meningitis E.coli have K1 antigen capsule.

(2) Endotoxin
- gram-negative sepsis-> fever, hypotension, & disseminated intravascular coagulation
- Th-17 helper T cells produce interleukin-17-> host defense against E. coli & Klebsiella sepsis.
- HIV Patients-> loss of Th-17 cells & predisposed to E. coli & Klebsiella sepsis.

Question 10

Clinical findings within intestinal tract

Answer 10

• ETEC-> watery diarrhea, non-bloody, self-limited, short duration
  (1–3 days).
• Associated traveler’s
  diarrhea/turista
• EHEC-> dysentery-> bloody diarrhea, abdominal cramping, &
  fever.
• STEC-> bloody diarrhea complicated by HUS
• kidney failure, hemolytic anemia,
  & thrombocytopenia.
• Hemolytic anemia-> by exotoxin-induced capillary damage-> damage to rbcs passing through capillaries.
• distorted, fragmented red cells->
  schistocytes->microangiopathic hemolytic anemia
• HUS-> children treated with fluoroquinolones for diarrhea and is why antibiotics not used to
  treat EHEC diarrhea.

Question 11

Clinical findings outside intestinal tract:

Answer 11

• UTIs-> women.
• 3 features facilitate ascending infection into bladder-> short urethra, proximity of urethra
  to anus, & colonization of vagina by members of fecal flora.
• Nosocomial (hospital-acquired) UTIs-> men & women
• use of indwelling urinary catheters.
• limited to bladder or extend up collecting system to kidneys.
• cystitis-> only bladder
• pain (dysuria) & frequency of urination; patients afebrile.
• pyelonephritis-> kidney
• fever, flank pain, & costovertebral angle tenderness; dysuria and frequency may or may not occur.
• meningitis and sepsis in neonates.
  -occurs during birth -> vaginal colonization.
• hospital-acquired sepsis-> urinary, biliary, or peritoneal infections.
• Peritonitis mixed infection by
  E. coli/other facultative enteric gram-negative rod plus
  anaerobic members of colonic flora (Bacteroides & Fusobacterium).

Question 12

Lab Diagnosis

Answer 12

• ferments lactose-> pink colonies; lactose-negative-> colorless.
• On EMB agar green colonies.
• Distinguishing Features from other lactose fermenting gram-negative rods:

(1) produces indole from tryptophan (2) decarboxylates lysine
(3) acetate as only carbon source
(4) motile.

• O157:H7 does not ferment sorbitol-> distinguishes it from other strains.

Question 13

Treatment

Answer 13

• depends on disease site & specific isolate’s resistance pattern.
• uncomplicated cystitis-> oral trimethoprimsulfamethoxazole
  or nitrofurantoin.
• Pyelonephritis-> ciprofloxacin or ceftriaxone.
• Sepsis-> parenteral antibiotics (3rd-gen cephalosporin [cefotaxime], with or without aminoglycoside [gentamicin]).
• Neonatal meningitis->ampicillin
  with cefotaxime.
• Diarrhea-> No Antibiotic therapy but trimethoprim-sulfamethoxazole or loperamide (Imodium) may shorten symptoms.
• Rehydration

Question 14

Prevention

Answer 14

• No active or passive immunization. - UTIs lowered by proper use & prompt withdrawal of catheters &
  recurrent infections-> prolonged prophylaxis with urinary antiseptic drugs (nitrofurantoin or trimethoprimsulfamethoxazole).
• cranberry juice
• Sepsis-> prompt removal or switching intravenous lines site.
• Traveler’s diarrhea-> doxycycline, ciprofloxacin, trimethoprim-sulfamethoxazole, or Pepto-Bismol.
• Ingestion of uncooked foods & unpurified water avoided while traveling in certain countries.