A peptide-binding domain shared with an Antarctic bacterium facilitates <i>Vibrio cholerae</i> human cell binding and intestinal colonization.

Abstract

<i>Vibrio cholerae,</i> the causative agent of the disease cholera, is responsible for multiple pandemics. <i>V. cholerae</i> binds to and colonizes the gastrointestinal tract within the human host, as well as various surfaces in the marine environment (e.g., zooplankton) during interepidemic periods. A large adhesin, the Flagellar Regulated Hemagglutinin A (FrhA), enhances binding to erythrocytes and epithelial cells and enhances intestinal colonization. We identified a peptide-binding domain (PBD) within FrhA that mediates hemagglutination, binding to epithelial cells, intestinal colonization, and facilitates biofilm formation. Intriguingly, this domain is also found in the ice-binding protein of the Antarctic bacterium <i>Marinomonas primoryensis</i>, where it mediates binding to diatoms. Peptide inhibitors of the <i>M. primoryensis</i> PBD inhibit <i>V. cholerae</i> binding to human cells as well as to diatoms and inhibit biofilm formation. Moreover, the <i>M. primoryensis</i> PBD inserted into FrhA allows <i>V. cholerae</i> to bind human cells and colonize the intestine and also enhances biofilm formation, demonstrating the interchangeability of the PBD from these bacteria. Importantly, peptide inhibitors of PBD reduce <i>V. cholerae</i> intestinal colonization in infant mice. These studies demonstrate how <i>V. cholerae</i> uses a PBD shared with a diatom-binding Antarctic bacterium to facilitate intestinal colonization in humans and biofilm formation in the environment.