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

Author:

Lloyd Cameron J.12,Guo Shuaiqi3,Kinrade Brett3,Zahiri Hossein3,Eves Robert3ORCID,Ali Syed Khalid12ORCID,Yildiz Fitnat4ORCID,Voets Ilja K.5ORCID,Davies Peter L.3,Klose Karl E.12ORCID

Affiliation:

1. South Texas Center for Emerging Infectious Diseases, University of Texas, San Antonio, TX 78249

2. Department of Molecular Microbiology and Immunology, University of Texas, San Antonio, TX 78249

3. Department of Biomedical and Molecular Sciences, Queen’s University, Kingston, ON K7L 3N6, Canada

4. Department of Microbiology and Environmental Toxicology, University of California, Santa Cruz, CA 95064

5. Laboratory of Macromolecular and Organic Chemistry, Eindhoven University of Technology, Eindhoven 5612, the Netherlands

Abstract

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.

Funder

San Antonio Area Foundation

Brown Foundation

Robert J. Kleberg, Jr. and Helen C. Kleberg Foundation

Gouvernement du Canada | Canadian Institutes of Health Research

Canada Research Chairs

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

Reference45 articles.

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