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Colonization factor CS3 is a critical surface protein complex found on enterotoxigenic Escherichia coli (ETEC), which is a primary cause of diarrheal disease in children in low-income countries and travelers (PubMed: 31405815). It belongs to the Colonization Factor Antigen II (CFA/II) group and consists of thin, flexible fibrillar structures that facilitate bacterial attachment to the small intestinal epithelium (UniProt: P0CK95). This adhesion is a prerequisite for the bacteria to colonize the gut and subsequently release heat-labile (LT) and heat-stable (ST) enterotoxins that cause fluid secretion and diarrhea (PubMed: 25701125). Due to its high prevalence among ETEC strains worldwide and its essential role in pathogenesis, CS3 is a major component in the development of multivalent ETEC vaccines, such as the oral inactivated vaccine ETVAX (PubMed: 33091357). Therapeutic strategies focus on inducing mucosal IgA antibodies that neutralize CS3, thereby preventing bacterial colonization and the onset of clinical symptoms.
Vaccine-induced mucosal secretory IgA antibodies bind to the CS3 protein on the bacterial surface, sterically hindering the attachment of enterotoxigenic Escherichia coli to intestinal epithelial receptors, thereby preventing colonization and subsequent toxin-mediated disease.
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