Diarrheagenic Escherichia coli
James P. Nataro* and James B. Kaper






Classic mechanisms of action of ETEC toxins (see the text for details and additional proposed mechanisms). (A) LT-I. The LT holotoxin, consisting of one A subunit and five B subunits, is internalized by epithelial cells of the small bowel mucosa via endocytosis. The A1, or catalytic, subunit translocates through the vacuolar membrane and passes through the Golgi apparatus by retrograde transport. In the figure, the A subunit is shown passing through the B subunit ring, but this may not be the case in vivo. A1 catalyzes the ADP-ribosylation of arginine 201 of the α subunit of Gs-protein (which may be apically located); the ADP-ribosylated G-protein activates adenylate cyclase, which elicits supranormal levels of intracellular cAMP. cAMP is an intracellular messenger which regulates several intestinal epithelial cell membrane transporters and other host cell enzymes, as well as having effects on the cytoskeleton. The activation of the cAMP-dependent A kinase results in phosphorylation of apical membrane transporters (especially the cystic fibrosis transmembrane conductance regulator), resulting in secretion of anions (predominantly Cl− by a direct effect, and HCO3 −indirectly) by crypt cells and a decrease in absorption of Na+ and Cl− by absorptive cells. cAMP may also have important effects on basolateral transporters and on intracellular calcium levels, both of which may increase the magnitude of the effects on fluid and ion transport. (B) STa. Less is known about the action of ST than of LT. ST is thought to act by binding the ST membrane receptor, GC-C. Activation of GC-C results in increased levels of intracellular cGMP. cGMP exerts its effects in increasing chloride secretion and decreasing NaCl absorption by activating the cGMP-dependent kinase (G-kinase) and/or the cAMP dependent kinase (A-kinase). Other effects of STa in inducing fluid secretion have also been postulated
SUMMARY
INTRODUCTION
ISOLATION AND IDENTIFICATION
Biochemicals
Serotyping
Phenotypic Assays Based on Virulence Characteristics
Molecular Detection Methods
Nucleic acid probes.
PCR.
COMMON THEMES IN E. COLI VIRULENCE
ENTEROTOXIGENIC E. COLI
Pathogenesis
Heat-labile toxins.
(i) LT-I.
(ii) LT-II.
Heat-stable toxins.
(i) STa.
(ii) STb.
Colonization factors.
Epidemiology
Clinical Considerations
Detection and Diagnosis
ENTEROPATHOGENIC E. COLI
Pathogenesis
Attaching-and-effacing histopathology.
Three-stage model of EPEC pathogenesis.
(i) Localized adherence.
(ii) Signal transduction.
(iii) Intimate adherence.
Secreted proteins.
Locus of enterocyte effacement.
EAF plasmids.
Regulation.
Other potential virulence factors.
(i) Other fimbriae.
(ii) EAST1.
(iii) Invasion.
Mechanism of diarrhea.
Epidemiology
Age distribution.
Transmission and reservoirs.
EPEC in developed countries.
EPEC in developing countries.
Clinical Considerations
Detection and Diagnosis
Definition of EPEC.
Diagnostic tests.
(i) Phenotypic tests.
(ii) Genotypic tests.
(a) eae gene.
(b) EAF plasmid.
ENTEROHEMORRHAGIC E. COLI
Origins
Pathogenesis
Histopathology.
Shiga toxins.
(i) Structure and genetics.
(ii) Stx in intestinal disease.
(iii) Stx in HUS.
EAST1.
Enterohemolysin.
Intestinal adherence factors.
pO157 plasmid.
Iron transport.
Other potential virulence factors.
Epidemiology
Incidence.
Animal reservoir.
Transmission.
Non-O157:H7 serotypes.
Clinical Considerations
Clinical disease.
Treatment.
Vaccines.
Diagnosis and Detection
General considerations.
(i) Why and when to culture.
(ii) Biosafety issues.
(iii) Diagnostic methods.
Culture techniques.
Immunoassays.
(i) O and H antigens.
(ii) Shiga toxins.
(iii) Other antigens.
(iv) Immunomagnetic separation.
(v) Free fecal cytotoxic activity.
DNA probes and PCR.
(i) Detection of stx genes.
(ii) Detection of eae genes.
(iii) Detection of the pO157 plasmid/hemolysin gene.
(iv) Detection of other genes.
Strain subtyping.
Serodiagnosis.
ENTEROAGGREGATIVE E. COLI
Pathogenesis
Histopathology.
Adherence.
EAST1.
Invasiveness.
Cytotoxins.
Model of EAEC pathogenesis.
Epidemiology
Clinical Features
Detection and Diagnosis
HEp-2 assay.
DNA probe.
Other tests for EAEC.
ENTEROINVASIVE E. COLI
Pathogenesis
Invasiveness.
Enterotoxin production.
Epidemiology
Clinical Considerations
Detection and Diagnosis
DIFFUSELY ADHERENT E. COLI
Pathogenesis
Epidemiology
Clinical Features
Detection and Diagnosis
OTHER CATEGORIES OF E. COLI WHICH ARE POTENTIALLY DIARRHEAGENIC
CONCLUSIONS
ACKNOWLEDGMENTS
REFERENCES

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