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Colonization factor CS6 is a major surface-exposed protein complex found on Enterotoxigenic Escherichia coli (ETEC), which is a leading cause of bacterial diarrhea in children in developing countries and travelers (Wolf et al., 1997, PubMed: 9353030). It belongs to a class of adhesins that facilitate the attachment of the bacteria to the human intestinal epithelium, a critical first step in the pathogenesis of ETEC infection (Svennerholm & Tobias, 2008, PubMed: 18445234). Unlike many other colonization factors that form long pili or fimbriae, CS6 is a non-fimbrial, heteropolymeric assembly composed of four distinct subunits: CssA, CssB, CssC, and CssD (UniProt: P0CK95, P0CK96). Because of its high prevalence in clinical ETEC isolates and its essential role in colonization, CS6 is a primary target for the development of oral vaccines, such as ETVAX, which aim to induce mucosal IgA antibodies that block bacterial adhesion (Lundgren et al., 2014, PubMed: 24935976). Therapeutic strategies focusing on CS6 involve both active immunization and the potential development of small-molecule inhibitors or monoclonal antibodies to disrupt the assembly or binding of the CS6 complex. The target is highly relevant for global health initiatives aimed at reducing the burden of diarrheal diseases (Qadri et al., 2005, PubMed: 15886834).
Induction of secretory IgA antibodies that bind to the CS6 complex, thereby sterically hindering the attachment of ETEC to the intestinal mucosa and preventing colonization (Svennerholm & Tobias, 2008, PubMed: 18445234).
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