Classification
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
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
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
- In urinary tract infections (UTIs):
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
| Pathogen | Pathogenesis/Virulence factor | Signs and Symptoms |
|---|---|---|
| ETEC |
|
No inflammation or invasion → traveler’s diarrhea (watery) |
| EPEC |
|
Mild inflammation → watery diarrhea with mucus |
| EAEC |
|
Mild inflammation → watery diarrhea |
| EHEC |
|
Severe inflammation → dysentery (bloody diarrhea) |
| EIEC | Direct invasion of the intestinal epithelium and formation of enterotoxins → necrosis and inflammation | Severe inflammation → dysentery (bloody diarrhea) similar to Shigella |
EPEC = enteropathogenic E. coli
EAEC = enteroaggregative E. coli
EHEC = enterohemorrhagic E. coli
EIEC = enteroinvasive E. coli
Enterotoxigenic E. coli (ETEC) pathogenesis:
Image by Lecturio.
The heat-stable (ST) enterotoxin causes cGMP accumulation in cells and secretion of fluid and electrolytes into the intestinal lumen.
The heat-labile (LT) enterotoxin acts like cholera toxin, which increases cAMP by activating adenylyl cyclase (AC).
General effect is water and chloride hypersecretion and inhibited sodium reabsorption.
Enterotoxigenic E. coli (ETEC) pathogenesis:
Image by Lecturio.
Noninvasive enterotoxins remain within the intestinal lumen and do not invade the epithelial cells.
Cfa: colonization factor antigen
Enteropathogenic E. coli (EPEC) pathogenesis:
Image by Lecturio.
EPEC uses intimin adhesion molecules to adhere to the intestinal cells. Binding causes cell deformation (brush border degeneration and loss of microvilli).
The characteristic effect of attachment, and effacement is thought to be the primary cause of diarrhea.
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
- 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
- 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/
- 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
- 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/
- Ryan, K. J. (Ed.). (2017). Sherris Medical Microbiology, 7th ed. McGraw-Hill. https://accessmedicine.mhmedical.com/content.aspx?bookid=2268§ionid=176087050
- 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
- Steffen, R. (2005). Epidemiology of traveler’s diarrhea. Clinical Infectious Diseases 41:536–540. https://pubmed.ncbi.nlm.nih.gov/16267715/
