Clinical implications of enteroadherent Escherichia coli

Abstract

Pathogenic Escherichia coli that colonize the small intestine primarily cause gastrointestinal illness in infants and travelers. The main categories of pathogenic E. coli that colonize the epithelial lining of the small intestine are enterotoxigenic E. coli, enteropathogenic E. coli, and enteroaggregative E. coli. These organisms accomplish their pathogenic process by a complex, coordinated multistage strategy, including nonintimate adherence mediated by various adhesins. These so called "enteroadherent E. coli" categories subsequently produce toxins or effector proteins that are either secreted to the milieu or injected to the host cell. Finally, destruction of the intestinal microvilli results from the intimate adherence or the toxic effect exerted over the epithelia, resulting in water secretion and diarrhea. In this review, we summarize the current state of knowledge regarding these enteroadherent E. coli strains and the present clinical understanding of how these organisms colonize the human intestine and cause disease.

Figure 1. ETEC-, EPEC- and EAEC-induced diarrhea is a multi-factorial event leading to disruption of ion/H₂O balance

(A) In an ETEC infection, the LT toxin (A₁ subunit) catalyzes the ADP-ribosylation of the α-subunit of G_s-protein, resulting in activation of adenylate cyclase and increased levels of intracellular cAMP. The activation of the cAMP-dependent A kinase results in phosphorylation of apical membrane transporters (i.e., the cystic fibrosis transmembrane conductance regulator, CFTR), resulting in secretion of Cl⁻ and HCO₃⁻ and decrease absorption of Na⁺ and Cl⁻. STa acts by binding to the GC-C membrane receptor. Activation of GC-C results in increased levels of intracellular cGMP, elevated Cl⁻ secretion and decreased Na absorption, due to activation of cGMP-dependent kinase (G-kinase) and/or the cAMP dependent kinase (A-kinase). (B) EPEC infection decreases epithelial ion absorption resulting in diarrhea as a result of the bacterial protein effectors secreted by the type III secretion system (TTSS) having an effect on Cl⁻ and Na⁺ ion activity. Some TTSS secreted proteins Esps) affecting ion balances are: EspF, inhibiting function of Na+/H+ exchange isoform 3 (NH3); EspG, disrupting microtubules and leading to decrease in apical Cl⁻/HCO3⁻ exchange activity. EPEC, via unknown effector molecules decrease butyrate (But) absorption and induced activation of protein tyrosine phosphatases (PTPases). This results in decreasing function of serotonin transporter (SERT) and increasing prostaglandin E -2 (PGE-2) and 5-hydroxytryptamine 5-HT) availability, further affecting ion absorption and motility, resulting in diarrhea. (C) EAEC produces two plasmid-encoded toxins, the E. coli heat stable enterotoxin (EAST) and the plasmid encoded-toxin (Pet). Further, the chromosomally-encoded protein involved in colonization (Pic) (not shown), the Shigella enterotoxin 1 (ShET1) and hemolysin E (HlyE) are also produced. Although several toxins are secreted by EAEC, the mechanism of action associated with the EAEC-mediated diarrheal disease has not been fully established but involves G-kinase and A-kinase-dependent mechanism.