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Colonization surface antigen 6 (CS6) is a critical non-fimbrial adhesin expressed on the surface of enterotoxigenic Escherichia coli (ETEC), which is a leading cause of moderate-to-severe diarrhea in children in developing countries and the most common cause of traveler's diarrhea (Svennerholm, 2011 [1]). Structurally, CS6 is a heteropolymer composed of two major subunits, CssA and CssB, which are essential for its assembly and functional attachment to human intestinal epithelial cells (Tobias et al., 2010 [2]). Unlike many other colonization factors that form long, hair-like pili, CS6 forms a thin, non-fimbrial coating on the bacterial surface that facilitates close-range adhesion (UniProt P0CK95 [4]). Because CS6 is one of the most frequently identified colonization factors in clinical ETEC isolates worldwide, it serves as a high-priority target for vaccine development (Lundgren et al., 2014 [3]). Current therapeutic strategies focus on oral inactivated vaccines, such as ETVAX, which are engineered to overexpress CS6 to elicit a robust mucosal IgA response (Qadri et al., 2019 [5]). By neutralizing CS6, the immune system can prevent the bacteria from colonizing the small intestine, thereby blocking the subsequent delivery of enterotoxins that cause disease symptoms.
Induction of protective mucosal secretory IgA antibodies that bind to the CS6 surface protein, thereby sterically hindering bacterial attachment to the intestinal epithelium and preventing colonization.
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