Enterotoxigenic Escherichia coli EtpA mediates adhesion between flagella and host cells

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Abstract
Enterotoxigenic Escherichia coli is the most common cause of diarrhoea in developing countries and is the principal cause of traveller's diarrhoea. Adhesion to host cells is essential for the virulence of this and many other bacterial pathogens. A new adhesion mechanism has been identified in E. coli that relies on the secreted protein EtpA. The protein interacts with conserved regions of flagellin molecules at the tips of the bacterial flagella where it forms an adhesive molecular bridge between the bacterium and the host cell. This finding adds to the evidence that EtpA — and the conserved flagellin ligands —could be viable antigenic targets for vaccines against E. coli and other motile pathogens. Adhesion to host cells is essential for virulence of many bacterial pathogens, including pathogenic Escherichia coli. An adhesion mechanism that relies on the secreted protein EtpA is now presented. EtpA attaches to both the bacterial flagella tip and the host cell, providing an adherence mechanism that is important for E. coli pathogenesis and may be present in many other pathogens that possess EtpA homologues. Adhesion to epithelial cells1 and flagella-mediated motility are critical virulence traits for many Gram-negative pathogens, including enterotoxigenic Escherichia coli (ETEC)2, a major cause of diarrhoea in travellers and children in developing countries3,4. Many flagellated pathogens export putative adhesins belonging to the two-partner secretion (TPS) family5. However, the actual function of these adhesins remains largely undefined. Here we demonstrate that EtpA, a TPS exoprotein adhesin of enterotoxigenic E. coli6, mimics and interacts with highly conserved regions of flagellin, the major subunit of flagella, and that these interactions are critical for adherence and intestinal colonization. Although conserved regions of flagellin are mostly buried in the flagellar shaft7, our results suggest that they are at least transiently exposed at the tips of flagella where they capture EtpA adhesin molecules for presentation to eukaryotic receptors. Similarity of EtpA to molecules encoded by other motile pathogens suggests a potential common pattern for bacterial adhesion, whereas participation of conserved regions of flagellin in adherence has implications for development of vaccines for Gram-negative pathogens.