Borrelial phosphomannose isomerase as a cell surface localized protein that retains enzymatic activity and promotes host-pathogen interaction
All organisms produce an intracellular enzyme, phosphomannose isomerase (PMI), that converts specific sugars during metabolism. Unexpectedly, we discovered an additional PMI function in <i>Borrelia burgdorferi</i>, the Lyme disease pathogen, where the enzyme is localized on the cell surface and binds to collagen IV-a host extracellular molecule mainly found in the skin. Low doses of PMI chemical inhibitors impair the growth of diverse strains of <i>B. burgdorferi</i> in culture, but not other tested bacterial pathogens. The passive transfer of anti-BbPMI antibodies in ticks can impact <i>B. burgdorferi</i> transmission to mice, while the treatment of collagen IV-containing murine skin with PMI inhibitors impairs infectivity. Taken together, these results highlight a newly discovered role for BbPMI in mediating host-pathogen interactions during infection. In turn, this discovery offers an opportunity for the development of a novel therapeutic strategy to combat Lyme disease by preventing BbPMI function and interaction with host collagen IV.
Authors
- Özlem Büyüktanır (ORCID: https://orcid.org/0000-0002-7641-7350)
- Yi‐Pin Lin (ORCID: https://orcid.org/0000-0002-5240-2031)
- Rachel M. Lipman (ORCID: https://orcid.org/0000-0002-0146-9738)
- Alexis A. Smith
- Brian T. Backstedt
- Michael Ronzetti (ORCID: https://orcid.org/0000-0001-5034-7692)
- Anil Kumar Shakya (ORCID: https://orcid.org/0000-0003-0637-652X)
- Vipin Singh Rana (ORCID: https://orcid.org/0000-0003-2673-7871)
- Shraboni Dutta (ORCID: https://orcid.org/0000-0002-8000-8111)
- Utpal Pal (ORCID: https://orcid.org/0000-0002-7504-4628)
- Ganesha Rai (ORCID: https://orcid.org/0000-0001-9763-9641)
- Chrysoula Kitsou
- Osnat Herzberg (ORCID: https://orcid.org/0000-0003-2823-7627)
- Sarai Araujo‐Aris
- Xiuli Yang (ORCID: https://orcid.org/0000-0002-7231-3167)
Institutions
- Tufts University (US)
- National Institutes of Health (US)
- Ondokuz Mayıs University (TR)
- Virginia–Maryland College of Veterinary Medicine (US)
- CIC bioGUNE (ES)
- National Center for Advancing Translational Sciences (US)
- Advanced Bioscience Laboratories (United States) (US)
- Digital Research Alliance of Canada
- Institute for Bioscience and Biotechnology Research
- University of Maryland, College Park (US)
Publication Details
- Journal
- mBio
- Published
- 2025-02-11
- DOI
- https://doi.org/10.1128/mbio.03609-24
- Citations
- 3
- Primary Topic
- Vector-borne infectious diseases
- Type
- article
- Field-Weighted Citation Impact
- 6.14
Funders
- U.S. Department of Health and Human Services
- National Institute of Allergy and Infectious Diseases
- National Center for Advancing Translational Sciences