Vaginal Lactobacillus fatty acid response mechanisms reveal a metabolite-targeted strategy for bacterial vaginosis treatment
Bacterial vaginosis (BV), a common syndrome characterized by Lactobacillus-deficient vaginal microbiota, is associated with adverse health outcomes. BV often recurs after standard antibiotic therapy in part because antibiotics promote microbiota dominance by Lactobacillus iners instead of Lactobacillus crispatus, which has more beneficial health associations. Strategies to promote L. crispatus and inhibit L. iners are thus needed. We show that oleic acid (OA) and similar long-chain fatty acids simultaneously inhibit L. iners and enhance L. crispatus growth. These phenotypes require OA-inducible genes conserved in L. crispatus and related lactobacilli, including an oleate hydratase (ohyA) and putative fatty acid efflux pump (farE). FarE mediates OA resistance, while OhyA is robustly active in the vaginal microbiota and enhances bacterial fitness by biochemically sequestering OA in a derivative form only ohyA-harboring organisms can exploit. OA promotes L. crispatus dominance more effectively than antibiotics in an in vitro BV model, suggesting a metabolite-based treatment approach.
Authors
- Charles O. Rock (ORCID: https://orcid.org/0000-0001-8648-4189)
- Vanessa Pillay
- Paul C. Blainey (ORCID: https://orcid.org/0000-0002-4889-8783)
- Meilin Zhu (ORCID: https://orcid.org/0000-0003-1302-4020)
- Seth M. Bloom (ORCID: https://orcid.org/0000-0002-0462-4596)
- Matthew W. Frank
- Thumbi Ndung’u (ORCID: https://orcid.org/0000-0003-2962-3992)
- Sarah Jeanfavre
- Joseph Elsherbini (ORCID: https://orcid.org/0000-0001-5995-2936)
- Amy Deik (ORCID: https://orcid.org/0000-0002-9687-0953)
- Clary B. Clish (ORCID: https://orcid.org/0000-0001-8259-9245)
- Fatima A. Hussain (ORCID: https://orcid.org/0000-0002-3669-795X)
- Nondumiso Xulu
- Christopher D. Radka (ORCID: https://orcid.org/0000-0002-6037-7710)
- Nasreen Khan
- Megan W. Tse (ORCID: https://orcid.org/0000-0002-4968-7072)
- Caroline M. Mitchell (ORCID: https://orcid.org/0000-0001-9924-2349)
- Julián Avila Pacheco
- Krista L. Dong (ORCID: https://orcid.org/0000-0002-2038-3518)
- Douglas S. Kwon (ORCID: https://orcid.org/0000-0001-8521-8735)
- Kerry A. Pierce (ORCID: https://orcid.org/0000-0001-8078-640X)
- Jiawu Xu (ORCID: https://orcid.org/0000-0002-0424-0736)
- Salina Hussain (ORCID: https://orcid.org/0009-0005-6166-4358)
- Jae Sun Kim
Institutions
- Broad Institute (US)
- St. Jude Children's Research Hospital (US)
- University of Kentucky (US)
- Ragon Institute of MGH, MIT and Harvard (US)
- Health Systems Trust (ZA)
- Africa Health Research Institute (ZA)
- University College London (GB)
- Massachusetts Institute of Technology (US)
- University of KwaZulu-Natal (ZA)
Publication Details
- Journal
- Cell
- Published
- 2024-08-19
- DOI
- https://doi.org/10.1016/j.cell.2024.07.029
- Citations
- 44
- Primary Topic
- Reproductive tract infections research
- Type
- article
- Field-Weighted Citation Impact
- 15.17
Funders
- National Science Foundation
- Bill and Melinda Gates Foundation
- St. Jude Children's Research Hospital
- American Lebanese Syrian Associated Charities
- Broad Institute
- Inyuvesi Yakwazulu-Natali
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases