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Escherichia coli colonization factors are adhesive structures, primarily fimbriae or pili, expressed by enterotoxigenic Escherichia coli (ETEC) to mediate attachment to the small intestinal epithelium, enabling bacterial colonization and subsequent toxin-mediated diarrhea. These factors, such as CFA/I (the archetype of class 5 fimbriae), CS1-CS6 (major CFs), and various minor CFs like CS14 and CS17, are assembled via chaperone-usher or alternate chaperone pathways, forming rigid helical filaments with a major subunit stalk and tip-localized minor adhesive subunit. They exhibit biophysical adaptations, including force-induced unwinding to sustain adhesion under shear stress in the intestinal niche, with CFA/I requiring the least force and distinguishing them from uropathogenic E. coli fimbriae. In disease, these factors are key virulence determinants in ETEC-associated traveler's diarrhea and pediatric infections in developing regions, with specific CFs like CFA/I, CS1-CS6 linked to moderate-to-severe diarrhea. Antigenic variation in surface-exposed residues evades host immunity, supporting repeated infections. No small-molecule drugs directly target these prokaryotic adhesins; instead, they are prioritized for vaccine strategies, including purified fimbriae, live attenuated strains, or epitope fusions to elicit anti-adhesive IgA antibodies blocking colonization.
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