Emerging and Underdetected Colonization Factors in Enterotoxigenic

Adhesionto the gut epithelium is the first step in ETEC infection and is mediated by colonization factors (CFs). CFs are also the main targets of the ETEC vaccines currently in development, which are based on a small set of CFs considered to be the most prevalent. However, a large proportion of clinical isolates are reported as CF-negative when screened with standard PCR panels. This is partly because ETEC adhesins are more diverse than previously appreciated, and partly because the methods used to detect them only screen for a small, historically defined set of CFs. These two explanations are difficult to separate, and both suggest that CF diversity, and with it the coverage of current CF-based vaccines, has likely been underestimated. This review examines emerging and underdetected CFs in human ETEC, focusing on κ- and γ-clade adhesins such as CS23 and their links to animal-associated fimbriae. It discusses the implications of this growing diversity for vaccine development, the need for continued surveillance as the CF landscape evolves, and approaches to achieving broader vaccine coverage across the expanding diversity of ETEC adhesins.