Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Enteroaggregative E. coli (EAEC) | Enterohemorrhagic E. coli (EHEC) | Enteroinvasive E. coli (EIEC) | Enteropathogenic E. coli (EPEC) | Enterotoxigenic E. coli (ETEC) | Epidemiology | Sites | Pathophysiology | Etiology | Clinical features | Diagnosis | Laboratory | Radiology description | Radiology images | Prognostic factors | Case reports | Treatment | Gross description | Microscopic (histologic) description | Microscopic (histologic) images | Positive stains | Electron microscopy description | Differential diagnosis | Additional references | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2 | Board review style question #3 | Board review style answer #3 | Board review style question #4 | Board review style answer #4 | Board review style question #5 | Board review style answer #5Cite this page: Bansal N. Escherichia coli. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/colonecoli.html. Accessed June 2nd, 2023.
Definition / general
- E. coli is a gram negative, facultative anaerobic, rod shaped bacteria
- E. coli is normal commensal of lower GI tract
- Most strains are non pathogenic but a few cause diseases in humans
- Pathogenic E. coli include 4 main subtypes
- Enteroaggregative E. coli (EAEC) cause diarrhea
- Enterohemorrhagic E. coli (EHEC) causes dysentery and hemolytic uremic syndrome
- Enteroinvasive E. coli (EIEC) cause acute self limited colitis
- Enterotoxigenic E. coli (ETEC) causes traveler's diarrhea
- also Enteropathogenic E. coli (EPEC) causes infant diarrhea in developing countries
- Most cases are transmitted through contaminated food and water
Essential features
- Most cases cause self limiting disease
- Treatment is supportive
Terminology
- Enterohemorrhagic E. coli, verocytotoxin producing E. coli, Shigatoxigenic Escherichia coli (STEC)
ICD coding
- B96.20 Infection due to Escherichia coli
Enteroaggregative E. coli (EAEC)
- Pattern of adherence characterized by self agglutination, called aggregative adherence, in a stacking pattern
- Affects children (usually < age 2 years) and adults, immunocompromised and HIV+ (developing and developed countries)
- Also immunocompetent and those without foreign travel
- EAEC adheres to intestinal mucosa and forms a mucoid biofilm
- Common cause of persistent watery diarrhea > 14 days (Clin Infect Dis 2006;43:402, J Infect Dis 1989;159:1061)
- Also fever, abdominal pain
- Laboratory: lactose fermenter, indole positive, citrate negative
- References: J Med Microbiol 2007;56:4, Lancet 1991;337:262, Koneman's Color Atlas and Textbook of Diagnostic Microbiology
Enterohemorrhagic E. coli (EHEC)
- Major foodborne pathogen (ground beef and salami, unpasteurized milk and juice, sprouts, lettuce)
- Also due to contact with cattle, swimming in contaminated waters
- Most common E. coli strain producing disease in U.S.
- Serotype O157:H7 is most commonly isolated strain, infectious dose is 100 bacterial cells or less
- Due to verotoxin, Shiga-like toxin in O157:H7 strains
- Symptoms: abrupt onset of abdominal pain, vomiting, and bloody diarrhea 3 - 4 days following ingestion with absence of fever
- Complications: up to 10% of patients, especially children under 15 years of age, may develop hemolytic uremic syndrome, usually 5 - 10 days after onset of diarrhea with up to 5% mortality rate
- Diagnosis: PCR (Mol Cell Probes 2006;20:31), enzyme immunoassay (J Clin Microbiol 2004;42:1652) or culture on Sorbitol MacConkey agar
- Laboratory: lactose fermenter, indole positive, citrate negative, colorless growth (sorbitol nonfermenter) on Sorbitol MacConkey
- Treatment: supportive therapy for HUS (platelets contraindicated), possibly with dialysis or plasmapheresis; avoid usage of anti-emetic or antiperistaltic agents; antibiotics not beneficial
- Microscopic description: necrosis of superficial mucosa, acute inflammation; necrotic foci may appear as pseudomembranous inflammation (usually not endoscopically visible); cryptitis and crypt abscesses; hemorrhage and edema in lamina propria, capillary thrombosis
- References: Iowa State University (pdf), Infect Immun 2007;75:4199, UpToDate, Stanford University
Enteroinvasive E. coli (EIEC)
- Causes dysentery-like syndrome with fever
- Due to contaminated food, water, or person to person spread
- Endemic to developing nations with rare outbreaks in industrialized countries
- Reported outbreaks in US primarily affect children under 5 years of age (Ryan: Sherris Medical Microbiology 2010 (5th ed), Ryan: Sherris Medical Microbiology 2003 (4th ed), pg 343 - 371)
- Infectious dose for health adults is 106
- Similar molecular features as Shigella (Infect Immun 2004;72:5080), due to virulence plasmid that encodes determinants (specific adhesion, outer membrane protein) for entry into epithelial cells and dissemination from cell to cell
- Invades and destroys colonic epithelium
- Laboratory: lactose fermenter and nonfermenters; lysine decarboxilase negative; nonmotile
- Treatment: generally self limited; fluid replacement as necessary; trimethoprim / sulfamethoxazole (TMP-SMX) or quinolones may reduce duration of diarrhea
- Micro images: bacterial invasion and destruction of colonic mucosa resulting in inflammation and ulceration
- References: Clin Microbiol Rev 1998;11:142, Am J Trop Med Hyg 2007;76:528, Todar's Online Textbook of Bacteriology
Enteropathogenic E. coli (EPEC)
- Some types of EPEC are known as diffusely adherent E. coli (DAEC)
- Major cause of infant diarrhea in developing countries
- Due to contaminated water and meat products
- Virulence mechanism is unrelated to excretion of typical E. coli enterotoxins - diarrhea and symptoms are caused by invasion of host cells ("attachment and effacement") rather than by production of toxins
- Has pathogenicity island that encodes proteins which modulate the actin microtubule and intermediate filament networks to allow intimate attachment of bacteria to plasma membrane of infected enterocytes, forming attachment and effacing lesions (J Bacteriol 2006;188:3110)
- Also has large plasmid containing cluster of genes encoding bundle forming pili
- Infectious dose is 106 organisms
- "Atypical" cases: (Emerg Infect Dis 2006;12:597) lack bundle forming pili, are associated with prolonged diarrhea
- Clinical features: infantile diarrhea may lead to dehydration, electrolyte imbalance or death; watery or bloody diarrhea; up to 50% mortality rates in developing countries
- Treatment: self limited; antibiotics may not improve disease and may increase the risk of developing hemolytic-uremic syndrome
- Micro description: effacement of brush border microvilli of enterocytes; no bacterial invasion but surface adherent organisms may be identifiable
- References: U.S. Food and Drug Administration, Todar's Online Textbook of Bacteriology, Microbiology 2004;150:527, Emerging Infectious Diseases 2002;8
Enterotoxigenic E. coli (ETEC)
- Annually causes 200 million diarrhea episodes and 170,000 to 380,000 deaths, due to contaminated food and water
- Most common cause of traveler diarrhea (Global burden map)
- Also a leading cause of infant diarrhea in developing countries
- An emerging cause of diarrhea in US (US burden map)
- Due to enterotoxins (heat labile and heat stable) produced by noninvasive bacteria that adhere to small intestine and produce cholera-like watery diarrhea
- Strains that can produce both enterotoxins cause more severe diarrhea
- Causes profuse watery diarrhea, abdominal cramping, fever, nausea
- Treatment: prophylaxis with rifaximin, careful food / beverage selection (Drugs 2006;66:303); rehydration; drugs vary based on current patterns of antimicrobial resistance; vaccines currently being tested (Clin Vaccine Immunol 2012;19:1921)
- Micro description: often do not cause inflammation due to noninvasive nature
- References: Clin Microbiol Rev 2006;19:583, Clin Microbiol Rev 2005;18:465, Centers for Disease Control
Epidemiology
- In USA most outbreaks have been reported in Minnesota, followed by Washington
- Route of transmission is foodborne; mainly by undercooked ground beef in EHEC (Emerg Infect Dis 2005;11:603)
- ETEC organisms are the principal cause of traveler's diarrhea and spread via contaminated food or water
- EIEC / EAEC organisms are bacteriologically similar to Shigella and are transmitted via food, water or by person to person contact
Sites
- Colon and rectum
Pathophysiology
- Depends on the strain of pathogenic E. coli
- Enteroaggregative E. coli
- EAEC adhere to epithelial cells
- EAEC attach to enterocytes via adherence fimbriae and are aided by dispersin, a bacterial surface protein that neutralizes the negative surface charge of lipopolysaccharide
- They also produce enterotoxins similar to Shigella enterotoxin and ETEC ST toxin
- Enterohemorrhagic E. coli
- EHEC are classified as E. coli O157:H7 and non O157:H7 serotypes
- Both serotypes produce Shiga-like toxins
- Hemolytic uremic syndrome (HUS) is caused by Shiga-like toxin which is absorbed by inflamed gastrointestinal mucosa into the circulation, where it alters endothelial cell function leading to platelet activation and aggregation
- Children and the elderly are at highest risk
- Enteroinvasive E. coli
- EIEC do not produce toxins, they invade epithelial cells and cause acute self limited colitis
- Enterotoxigenic E. coli
- ETEC produce heat labile toxin (LT) and heat stable toxin (ST)
- Both induce chloride and water secretion while inhibiting intestinal fluid absorption
- The LT toxin activates adenylate cyclase and stimulates chloride secretion and simultaneously inhibits absorption
- ST toxins bind to guanylate cyclase and stimulate chloride secretion
- Enteroaggregative E. coli
Etiology
- Contaminated food and water
Clinical features
- EAEC organisms cause nonbloody diarrhea that may be prolonged in AIDS patients
- They cause large outbreaks of bloody diarrhea and HUS
- HUS includes microangiopathic hemolytic anemia and thrombocytopenia but no neurologic symptoms and no acute renal failure
- Also causes traveler's diarrhea and diarrhea in both children and adults
- Secretory, noninflammatory diarrhea, vomiting, dehydration and in severe cases, shock
Diagnosis
- Typically made by clinical findings and history of ingestion of contaminated food like undercooked meat
Laboratory
- A stool culture on sorbitol MacConkey agar (SMAC) or the variant cefixime potassium tellurite sorbitol MacConkey agar (CT-SMAC)
- Colonies appear clear on SMAC due to their inability to ferment sorbitol, while sorbitol fermenting colonies of E. coli serotypes appear red
- E. coli DNA extraction method: DNA probes plus PCR techniques for detecting verocytotoxin
Radiology description
- CT usually preferred modality for radiological assessment (AJR Am J Roentgenol 2001;177:619)
- Shows severe diffuse colonic wall thickening, often with a target sign and pericolic stranding
- Involvement of bowel can be segmental or diffuse
Radiology images
Prognostic factors
- Disease is usually self limiting, and patients recover on supportive therapy
Case reports
- 4 month old boy with EIEC severe dysentery complicated by rotavirus gastroenteritis (J Infect 2006;53:e211)
- Two children with EIEC 0144:NM infection and encephalopathy (J Clin Microbiol 1996;34:2432)
- 28 year old man with enteroinvasive Klebsiella pneumoniae and Escherichia coli sepsis from a contaminated hamburger (Am J Gastroenterol 1998;93:118)
- 32 year old HIV+ man with bacteremia (J Clin Microbiol 1991;29:2675)
- 43 year old HIV+ man with diarrhea (N Engl J Med 1995;332:273)
- 1991, Oregon, due to swallowing contaminated lake water (N Engl J Med 1994;331:579)
- 1992 - 3, Washington State, due to uncooked hamburger meat (JAMA 1994;272:1349, West J Med 1996;165:15)
- 2002, Alberta Canada, due to unpasteurized gouda cheese (Can J Public Health 2005;96:182)
Treatment
- Treatment is mainly supportive
- Antibiotic use with STEC infections is not recommended (Clin Infect Dis 2016;62:1251)
Gross description
- EHEC: colonic mucosa is edematous and erythematous with multiple erosions
- Erosion may show adherent blood clots
Microscopic (histologic) description
- EAEC, EIEC, ETEC:
- No significant microscopic changes
- EHEC:
- Foci of epithelial cell damage / necrosis with pyknotic nuclei, vacuolated cytoplasm
- Areas of hemorrhage within lamina propria
- Gram negative bacterial rods could be found on the apical surfaces of mucosal epithelial cells
Microscopic (histologic) images
Positive stains
- E. coli are gram negative bacilli
Electron microscopy description
- TEM, in cases of EHEC, shows pyknotic nuclei, damaged membranes and cytoplasmic vacuolization of colonic epithelial cells
Differential diagnosis
- Ischemic Colitis: negative culture for E. coli; no significant history
- Other infective colitis: negative culture for E. coli
Additional references
- The role of Escherichia coli in inflammatory bowel disease (Gut 2007;56:610)
- Risk factors for the hemolytic uremic syndrome in children infected with Escherichia coli (Clin Infect Dis 2012;55:33)
- Hemorrhagic colitis associated with EHEC in a heifer (JMM Case Rep 2015;2:e005004)
Board review style question #1
What are different pathogenic strains of E. coli?
- Enteroaggregative E. coli
- Enterohemorrhagic E. coli
- Enteroinvasive E. coli
- Enterotoxigenic E. coli
- All of the above
Board review style answer #1
Board review style question #2
Traveler’s diarrhea is mostly caused by which strain?
- Enteroaggregative E. coli
- Enterohemorrhagic E. coli
- Enteroinvasive E. coli
- Enterotoxigenic E. coli
Board review style answer #2
Board review style question #3
Which E. coli strain cause symptoms similar to S. dysenteriae?
- Enteroaggregative E. coli
- Enterohemorrhagic E. coli
- Enteroinvasive E. coli
- Enterotoxigenic E. coli
Board review style answer #3
Board review style question #4
Hemolytic uremic syndrome (HUS) is caused by which E. coli strain?
- Enteroaggregative E. coli
- Enterohemorrhagic E. coli O157:H7
- Enteroinvasive E. coli
- Enterotoxigenic E. coli
Board review style answer #4
Board review style question #5
What are clinical features of HUS?
- Microangiopathic hemolytic anemia
- Occurs usually in children
- Thrombocytopenia
- All of the above
Board review style answer #5