Vaccination with EtpA glycoprotein or flagellin protects against colonization with enterotoxigenic Escherichia coli in a murine model.

Enterotoxigenic Escherichia coli (ETEC) remain a leading cause diarrheal illness, prompting a search for vaccine targets that led to the recent discovery of EtpA, a secreted adhesin of ETEC that acts by bridging flagella and host cells. In a murine model, immunization with recombinant EtpA glycoprotein inhibited colonization by two EtpA-producing human ETEC strains, H10407 and E24377A. In addition, vaccination with recombinant flagellin (serotype H11) generated antibodies that specifically recognized the tips of flagella from E24377A expressing a heterologous flagellar serotype (H28) and afforded significant protection against colonization. EtpA and/or flagellin could be valuable subunit antigens in the formulation of a broadly protective ETEC vaccine.

Enterotoxigenic Escherichia coli EtpA mediates adhesion between flagella and host cells.

Adhesion to epithelial cells and flagella-mediated motility are critical virulence traits for many Gram-negative pathogens, including enterotoxigenic Escherichia coli (ETEC), a major cause of diarrhoea in travellers and children in developing countries. Many flagellated pathogens export putative adhesins belonging to the two-partner secretion (TPS) family. However, the actual function of these adhesins remains largely undefined. Here we demonstrate that EtpA, a TPS exoprotein adhesin of enterotoxigenic E. coli, 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 shaft, 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.