Broadly conserved FlgV controls flagellar assembly and Borrelia burgdorferi dissemination in mice
Flagella propel pathogens through their environments, yet are expensive to synthesize and are immunogenic. Thus, complex hierarchical regulatory networks control flagellar gene expression. Spirochetes are highly motile bacteria, but peculiarly, the archetypal flagellar regulator σ<sup>28</sup> is absent in the Lyme spirochete Borrelia burgdorferi. Here, we show that gene bb0268 (flgV) in B. burgdorferi, previously and incorrectly annotated to encode the RNA-binding protein Hfq, is instead a structural flagellar component that modulates flagellar assembly. The flgV gene is broadly conserved in the flagellar superoperon alongside σ<sup>28</sup> in many Spirochaetae, Firmicutes and other phyla, with distant homologs in Epsilonproteobacteria. We find that B. burgdorferi FlgV is localized within flagellar basal bodies, and strains lacking flgV produce fewer and shorter flagellar filaments and are defective in cell division and motility. During the enzootic cycle, flgV-deficient B. burgdorferi survive and replicate in Ixodes ticks but are attenuated for infection and dissemination in mice. Our work defines infection timepoints when spirochete motility is most crucial and implicates FlgV as a broadly distributed structural flagellar component that modulates flagellar assembly.
Authors
- Daniel Soliman (ORCID: https://orcid.org/0000-0001-8380-2970)
- Yuen‐Yan Chang (ORCID: https://orcid.org/0000-0003-4952-8941)
- Philip P. Adams (ORCID: https://orcid.org/0000-0002-2575-6328)
- L. Aravind (ORCID: https://orcid.org/0000-0003-0771-253X)
- Gisela Storz
- Amanda G. Lasseter (ORCID: https://orcid.org/0000-0003-1859-4065)
- Maxime Zamba‐Campero
- Mollie W. Jewett (ORCID: https://orcid.org/0000-0003-3130-3795)
- Jeffrey A. Silberman (ORCID: https://orcid.org/0009-0007-6802-2002)
- Jun Liu (ORCID: https://orcid.org/0000-0003-3108-6735)
- Huaxin Yu
Institutions
- University of Central Florida (US)
- National Institutes of Health (US)
- United States National Library of Medicine (US)
- Yale University (US)
- National Institute of Nursing Research (US)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (US)
- Office of Extramural Research (US)
- National Institute of General Medical Sciences (US)
- Florida College (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-11-29
- DOI
- https://doi.org/10.1038/s41467-024-54806-w
- Citations
- 6
- Primary Topic
- Vector-borne infectious diseases
- Type
- article
- Field-Weighted Citation Impact
- 3.09
Funders
- Yale University
- Fonds National de la Recherche Luxembourg
- National Institutes of Health
- National Institute of General Medical Sciences
- National Institute of Allergy and Infectious Diseases
- National Institute of Child Health and Human Development
- U.S. National Library of Medicine
- Eunice Kennedy Shriver National Institute of Child Health and Human Development