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Colonization surface antigen 6 (CS6) is a major non-fimbrial adhesin expressed by Enterotoxigenic Escherichia coli (ETEC), a leading cause of bacterial diarrhea in children and travelers (Svennerholm, 2017). The CS6 complex is composed of four proteins—CssA, CssB, CssC, and CssD—where CssA and CssB serve as the structural subunits that facilitate binding to the host intestinal epithelium (Wolf et al., 1997; UniProt P0CK95). Unlike many other ETEC colonization factors that form long fimbriae, CS6 forms a thin, non-fimbrial coating on the bacterial surface (Tobias et al., 2010). Its primary biological function is to mediate the adherence of ETEC to the small intestine, which is a prerequisite for the delivery of enterotoxins that cause fluid secretion and diarrhea (Qadri et al., 2005). Because of its high prevalence in clinical ETEC strains, CS6 is a critical target for vaccine development, notably in the oral inactivated vaccine ETVAX (Lundgren et al., 2014). Therapeutic strategies focus on inducing mucosal IgA antibodies that sterically hinder CS6-mediated attachment, thereby preventing infection.
Induction of mucosal secretory IgA antibodies that bind to the CS6 complex, preventing bacterial attachment to the intestinal epithelium and subsequent toxin delivery.
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