A peptide-binding domain shared with an Antarctic bacterium facilitates Vibrio cholerae human cell binding and intestinal colonization

• Published in: Proceedings of the National Academy of Sciences
• Main Authors: Lloyd, Cameron J., Guo, Shuaiqi, Kinrade, Brett, Zahiri, Hossein, Eves, Robert, Ali, Syed Khalid, Yildiz, Fitnat, Voets, Ilja K., Davies, Peter L., Klose, Karl E.
• Format: Article in Journal/Newspaper
• Language: English
• Published: 2023
• Subjects: adhesin; cholera; peptide-binding; Intestines; Gastrointestinal Tract; Humans; Vibrio cholerae/genetics; Infant; Animals; Cell Aggregation; Bacteria; Mice; Diatoms; /dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being; name=SDG 3 - Good Health and Well-being; /dk/atira/pure/sustainabledevelopmentgoals/life_below_water; name=SDG 14 - Life Below Water; Antarctic; The Antarctic; Antarc*
• Online Access: https://research.tue.nl/en/publications/449d9f03-ef19-4177-9ebd-35565e18f1b6; https://doi.org/10.1073/pnas.2308238120; https://pure.tue.nl/ws/files/312666588/lloyd-et-al-2023-a-peptide-binding-domain-shared-with-an-antarctic-bacterium-facilitates-vibrio-cholerae-human-cell.pdf; http://www.scopus.com/inward/record.url?scp=85171811782&partnerID=8YFLogxK

Vibrio cholerae, the causative agent of the disease cholera, is responsible for multiple pandemics. V. cholerae 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 Marinomonas primoryensis, where it mediates binding to diatoms. Peptide inhibitors of the M. primoryensis PBD inhibit V. cholerae binding to human cells as well as to diatoms and inhibit biofilm formation. Moreover, the M. primoryensis PBD inserted into FrhA allows V. cholerae 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 V. cholerae intestinal colonization in infant mice. These studies demonstrate how V. cholerae uses a PBD shared with a diatom-binding Antarctic bacterium to facilitate intestinal colonization in humans and biofilm formation in the environment.