Colon

• 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+ (in 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: Koneman's Color Atlas and Textbook of Diagnostic Microbiology, 6th Edition, 2005

• 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 the 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 (HUS), usually 5 - 10 days after onset of diarrhea with up to 5% mortality rate
• Diagnosis: PCR, enzyme immunoassay or culture on sorbitol MacConkey agar (Mol Cell Probes 2006;20:31, J Clin Microbiol 2004;42:1652)
• 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 antiemetic or antiperistaltic agents
  • Antibiotics are 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: Enterohemorrhagic Escherichia coli and Other E. coli Causing Hemolytic Uremic Syndrome [Accessed 22 February 2023], Infect Immun 2007;75:4199, UpToDate: Shiga Toxin-Producing Escherichia coli - Clinical Manifestations, Diagnosis, and Treatment [Accessed 22 February 2023], Stanford University: Enterohemorrhagic E coli Colitis [Accessed 22 February 2023]

• 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 the U.S. primarily affect children under 5 years of age (Ryan: Sherris Medical Microbiology, 5th Edition, 2010, Ryan: Sherris Medical Microbiology, 4th Edition, 2003)
• Infectious dose for healthy adults is 10⁶
• Similar molecular features to Shigella, due to virulence plasmid that encodes determinants (specific adhesion, outer membrane protein) for entry into epithelial cells and dissemination from cell to cell (Infect Immun 2004;72:5080)
• 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 description: 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: Todar's Online Textbook of Bacteriology, 2020

• 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 that contains a cluster of genes encoding bundle forming pili
• Infectious dose is 10⁶ organisms
• Atypical cases lack bundle forming pili and are associated with prolonged diarrhea (Emerg Infect Dis 2006;12:597)
• 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: Food and Drug Administration: Bad Bug Book - Foodborne Pathogenic Microorganisms and Natural Toxins, 2nd Edition, 2012, Todar: Todar's Online Textbook of Bacteriology, 2020, Microbiology (Reading) 2004;150:527, Emerg Infect Dis 2002;8:508

• Annually causes 200 million diarrhea episodes and 170,000 to 380,000 deaths, due to contaminated food and water
• Most common cause of traveler's diarrhea (CDC: Enterotoxigenic E. coli (ETEC) [Accessed 15 March 2023])
• Also a leading cause of infant diarrhea in developing countries
• Emerging cause of diarrhea in the U.S. (Rev Environ Health 2008;23:135)
• Due to enterotoxins (heat labile [LT] and heat stable [ST]) 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, rehydration
  • Drugs vary based on current patterns of antimicrobial resistance; vaccines are currently being tested (Drugs 2006;66:303, Clin Vaccine Immunol 2012;19:1921)
• Micro description: often does not cause inflammation due to its noninvasive nature
• References: Clin Microbiol Rev 2006;19:583, Clin Microbiol Rev 2005;18:465, CDC: Enterotoxigenic E. coli (ETEC) [Accessed 22 February 2023]

• EAEC organisms cause nonbloody diarrhea that may be prolonged in AIDS patients (Am J Trop Med Hyg 2010;83:158)
• EHEC causes symptoms similar to S. dysenteriae
  • Causes large outbreaks of bloody diarrhea and HUS
  • HUS includes microangiopathic hemolytic anemia and thrombocytopenia but no neurologic symptoms and no acute renal failure (Med Clin North Am 2013;97:681)
• EIEC is common among young children in developing countries
  • Also causes traveler's diarrhea and diarrhea in both children and adults (J Vet Sci 2022;23:e28)
• ETEC causes traveler's diarrhea commonly in underdeveloped regions and children younger than 2 years of age are particularly susceptible
  • Secretory, noninflammatory diarrhea, vomiting, dehydration and in severe cases, shock (Gut Microbes 2022;14:2055943)

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Contributed by Ateeqa Mujeeb Ullah, M.D.

Contributed by Ateeqa Mujeeb Ullah, M.D.

Which E. coli strain has been implicated as a possible precursor to the development of colorectal cancer?

1. Adherent invasive E. coli (AIEC)
2. Diffusely adherent E. coli (DEAC)
3. Enteropathogenic E. coli (EPEC)
4. Enterotoxigenic E. coli (ETEC)
5. Shiga toxin producing E. coli (STEC)

B. Diffusely adherent E. coli (DEAC). Diffusely adherent E. coli (DEAC) found in colons of Crohn's disease and colorectal cancer (CRC) patients have been found to harbor the daaC and afaBC genes. The afa1 positive strains isolated from these patients demonstrate adherence and invasion into various epithelial cells and also induce the increased mRNA expression of VEGF (vascular endothelial growth factor), which promotes angiogenesis in tumors. Multiple other genes and the proinflammatory effect of DEAC adhesions on intestinal epithelium has also been associated with the development of Crohn's disease and CRC according to multiple studies (Gastroenterology 2004;127:80, Advancements of Microbiology 2019;58:143, World J Gastrointest Pathophysiol 2014;5:213). No other strain of E. coli has been associated with the development of CRC.

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Reference: Escherichia coli

A 45 year old woman with chronic kidney disease status post renal transplant presents to the emergency department with vomiting, bloody diarrhea and dehydration. In light of the recent E. coli O157:H7 outbreak, you suspect E. coli colitis. What is the gold standard for diagnosis?

1. Cefixime potassium tellurite sorbitol MacConkey agar (CT SMAC)
2. Horse blood agar
3. Thayer Martin Agar (VPN agar)
4. Thiosulfate citrate bile salts sucrose agar (TCBS)

A. Cefixime potassium tellurite sorbitol MacConkey agar (CT SMAC). Cefixime potassium tellurite sorbitol MacConkey agar (CT SMAC) is a modified form of MacConkey sorbitol agar (SMAC) that contains selective agents cefixime and tellurite. Cefixime inhibits the growth of other enteric organisms, such as Proteus spp. and potassium tellurite inhibits non-O157 Shiga toxin producing E. coli (STEC). The use of CT SMAC has been associated with increased cultural sensitivity for the isolation of E. coli O157:H7. Therefore, it is recommended by the American Society of Microbiology and Centers for Disease Control and Prevention (CDC) for use as a primary isolation medium for E. coli O157:H7 in community acquired diarrhea (Versalovic: Manual of Clinical Microbiology, 10th Edition, 2011). The mechanism includes the production of pink colonies by E. coli strains other than O157:H7 through the fermentation of D sorbitol, whereas the colonies of CT SMAC are colorless after overnight incubation due to the lack of D sorbitol fermentation (ThermoFisher: MacConkey Sorbitol Agar w/ Cefixime and Tellurite [Accessed 15 March 2023).

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Reference: Escherichia coli