Escherichia coli

The gram-negative bacterium Escherichia coli is a key component of the human gut microbiota. Most strains of E. coli are avirulent, but occasionally they escape the GI tract, infecting the urinary tract and other sites. Less common strains of E. coli are able to cause disease within the GI tract, most commonly presenting as abdominal pain and diarrhea. E. coli is transmitted via a fecal–oral route, which can occur with unsanitary food preparation, contamination of meat or produce by manure, irrigating or washing crops/fruits with contaminated water, and consumption of contaminated water.

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Classification

Gram negative bacteria classification flowchart

Gram-negative bacteria:
Most bacteria can be classified according to a lab procedure called Gram staining.
Bacteria with cell walls that have a thin layer of peptidoglycan do not retain the crystal violet stain utilized in Gram staining. These bacteria do, however, retain the safranin counterstain and thus appear as pinkish-red on the stain, making them gram negative. These bacteria can be further classified according to morphology (diplococci, curved rods, bacilli, and coccobacilli) and their ability to grow in the presence of oxygen (aerobic versus anaerobic). The bacteria can be more narrowly identified by growing them on specific media (triple sugar iron (TSI) agar) where their enzymes can be identified (urease, oxidase) and their ability to ferment lactose can be tested.
* Stains poorly on Gram stain
** Pleomorphic rod/coccobacillus
*** Require special transport media

Image by Lecturio.

General Characteristics

  • Features:
    • Stain: gram-negative
    • Morphology: bacillus (rod)
    • Facultative anaerobic
    • Either nonmotile or motile (flagellated)
    • Catalase-positive
    • Ferments lactose 
  • Special media and biochemical test:
    • MacConkey agar: grows as pink colonies
    • Eosin–methylene blue (EMB) agar: grows as metallic, green colonies
    • Indole test–positive
Photomicrograph of Escherichia coli

Photomicrograph of Escherichia coli

Image: “E. coli Bacteria” by NIAID. License: CC BY 2.0

Pathogenesis and Virulence Factors

Virulence

  • Antigenic structures:
    • O antigen: component of the lipopolysaccharide (LPS) in the cell wall
    • H antigen: flagellar protein
    • K antigen: polysaccharide capsule 
  • Adherence factors and toxins are specific to the E. coli strain.

Avirulent variants of Escherichia coli

  • Reservoir:
    • Humans are the primary reservoir.
    • Strains are part of the normal gut flora.
  • Transmission:
    • In urinary tract infections (UTIs):
      • Bacterium ascends urethra to cause infection. 
      • More common in women or with catheter use
      • Type 1 fimbriae (pili): virulence factor that allows bacterial attachment to uroepithelial cells.
    • In neonatal meningitis:
      • Infant infected with maternal E. coli through rupture of membranes or during childbirth
      • K1 capsular polysaccharide: virulence factor in most cases

Pathogenic variants of Escherichia coli

  • Pathogenic strains are found exogenously and are introduced through unsanitary food production or preparation.
  • Transmission:
    • Fecal–oral route
    • Contaminated meat or produce
  • Employ various virulence factors in producing illness, depending on the pathogen
Table: Pathogenic variants of E. coli
PathogenPathogenesis/Virulence factorSigns and Symptoms
ETEC
  • Fimbrial adhesins allow binding to the intestinal mucosa
  • Heat-labile (LT) enterotoxin increases cAMP → altered electrolyte transport (↑ chloride secretion) and diarrhea
  • LT: related to cholera toxin
  • Heat-stabile (ST) enterotoxin increases cGMP → diarrhea
  • No inflammation or invasion
No inflammation or invasion → traveler’s diarrhea (watery)
EPEC
  • For colonization, requires bundle-forming pilus (BFP) (encoded by a plasmid EPEC adherence factor or EAF)
  • Carries chromosomal locus of enterocyte effacement (LEE), which encodes intimin, a specific adhesin that binds intestinal epithelium
  • No toxin production
Mild inflammation → watery diarrhea with mucus
EAEC
  • Aggregative adherence fimbriae (AAF) to adhere to intestinal mucosa; forms a biofilm
  • “Stacked-brick” adherence pattern
  • Some possess a heat-stable (ST) enterotoxin, similar to ETEC.
Mild inflammation → watery diarrhea
EHEC
  • Binds to intestinal epithelium via bacterial fimbriae
  • Employs phage-encoded Shiga toxin:
    • Cytotoxic to both intestinal villi and colon epithelial cells
    • Inhibits protein synthesis → cell death
  • O157:H7 strain may lead to hemolytic uremic syndrome.
Severe inflammation → dysentery (bloody diarrhea)
EIECDirect invasion of the intestinal epithelium and formation of enterotoxins → necrosis and inflammationSevere inflammation → dysentery (bloody diarrhea) similar to Shigella
ETEC = enterotoxigenic E. coli
EPEC = enteropathogenic E. coli
EAEC = enteroaggregative E. coli
EHEC = enterohemorrhagic E. coli
EIEC = enteroinvasive E. coli

Associated Diseases

Urinary tract infections

  • E. coli is the leading cause of UTIs in women.
  • Diagnosis: urinalysis with urine culture
  • Treatment: antibiotics (e.g., nitrofurantoin, trimethoprim–sulfamethoxazole)

Neonatal meningitis

  • E. coli can cause meningitis and sepsis (which often coexist, or sepsis may precede meningitis).
  • Signs and symptoms:
    • Fever
    • Full fontanelles
    • Vomiting
    • Coma
    • Convulsions
    • Poor or absent Moro reflex
    • Hypertonia or hypotonia
  • Diagnosis: CSF analysis showing leukocytosis and low glucose and bacteria on Gram stain
  • Treatment: antibiotics (e.g., ceftriaxone)

Diarrhea

  • Enterotoxigenic E. coli (ETEC):
    • Most common cause of traveler’s diarrhea worldwide
    • Diarrhea usually in resource-limited settings (especially with sanitation problems)
    • Short incubation period, lasting ≤ 5 days
    • Watery, secretory diarrhea, with nausea, cramping:
      • Similar to cholera
      • Diarrhea from ETEC is rice-colored.
      • Patients can lose up to 20 L of fluid a day.
    • Diagnosis: detection of heat-labile or heat-stable enterotoxins (by polymerase chain reaction (PCR))
    • Treatment is supportive.
  • Enteropathogenic E. coli (EPEC):
    • EPEC is a major cause of sporadic watery diarrhea in children (mostly < 2 years of age) in developing countries.
    • Watery diarrhea without blood nor pus
    • Diagnosis: stool PCR
    • Treatment is supportive.
  • Enteroaggregative E. coli (EAEC):
    • EAEC is the second most common cause of traveler’s diarrhea.
    • Results in both acute and chronic watery diarrhea in patients with HIV and AIDS 
    • Treatment: fluoroquinolones to prevent chronic infection
  • Enterohemorrhagic E. coli (EHEC):
    • Primarily a food-borne infection
    • Painful, bloody diarrhea
    • Infection with strain O157:H7 can lead to hemolytic uremic syndrome (HUS), a triad of:
      • Hemolytic anemia
      • Thrombocytopenia
      • AKI
    • Children are more likely to develop HUS than adults.
    • Diagnosis: detection of Shiga toxin by enzyme immunoassay or PCR
    • Treatment:
      • Supportive
      • Avoid antibiotics, as they have been associated with the development of HUS.
  • Enteroinvasive E. coli (EIEC):
    • Seen in travelers to and children in developing countries 
    • EIEC directly invades the intestinal epithelium, causing bloody diarrhea.
    • Treatment is supportive.

References

  1. Holtz, L. R., Tarr, P. I. (2021). Shiga toxin-producing Escherichia coli: clinical manifestations, diagnosis, and treatment. UpToDate. Retrieved April 26, 2021, from https://www.uptodate.com/contents/shiga-toxin-producing-escherichia-coli-clinical-manifestations-diagnosis-and-treatment
  2. Johnson, J. R. (1991). Virulence factors in Escherichia coli urinary tract infection. Clinical Microbiology Reviews 4:80–128. https://pubmed.ncbi.nlm.nih.gov/1672263/
  3. Nataro, J. P., Calderwood, S. B. (2020). Pathogenic Escherichia coli associated with diarrhea. UpToDate. Retrieved April 26, 2021, from https://www.uptodate.com/contents/pathogenic-escherichia-coli-associated-with-diarrhea
  4. Nguyen, Y., Sperandio, V. (2012). Enterohemorrhagic E. coli (EHEC) pathogenesis. Frontiers in Cellular and Infection Microbiology 12:90. https://pubmed.ncbi.nlm.nih.gov/22919681/
  5. Ryan, K. J. (Ed.). (2017). Sherris Medical Microbiology, 7th ed. McGraw-Hill. https://accessmedicine.mhmedical.com/content.aspx?bookid=2268&sectionid=176087050
  6. Sarowska, J., Futoma-Koloch, B., Jama-Kmiecik, A., et al. (2019). Virulence factors, prevalence and potential transmission of extraintestinal pathogenic Escherichia coli isolated from different sources: recent reports. Gut Pathogens 11(10). https://doi.org/10.1186/s13099-019-0290-0 
  7. Steffen, R. (2005). Epidemiology of traveler’s diarrhea. Clinical Infectious Diseases 41:536–540. https://pubmed.ncbi.nlm.nih.gov/16267715/

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