Cited by 61Reproductive tract infections researchGut microbiota and healthProbiotics and Fermented Foods

Vaginal Lactobacillus fatty acid response mechanisms reveal a metabolite-targeted strategy for bacterial vaginosis treatment

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Zhu, Meilin, Frank, Matthew W., Radka, Christopher D., Jeanfavre, Sarah, Xu, Jiawu, Tse, Megan W., Pacheco, Julian Avila, Kim, Jae Sun +16 more·2024·Cell

Abstract

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.

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  1. [67]Dayan N. Wertz P.W. Innate Immune System of Skin and Oral Mucosa: Properties and Impact in Pharmaceutics, Cosmetics, and Personal Care Products 2011 John Wiley & Sons
  2. [87]Rampersaud R. Identifcation and characterization of Inerolysin, the cholesterol dependent cytolysin Produced Lactobacillus Iners 2014 10.7916/D8P26W2V PMC3067590 21169489 · DOI
  3. [108]Edgar R.C. MUSCLE v5 enables improved estimates of phylogenetic tree confidence by ensemble bootstrapping Preprint at bioRxiv 2021 10.1101/2021.06.20.449169 · DOI

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Authors
Zhu, M., Frank, M. W., Radka, C. D., Jeanfavre, S., Xu, J., Tse, M. W., Pacheco, J. A., Kim, J. S., Pierce, K., Deik, A., Hussain, F. A., Elsherbini, J., Hussain, S., Xulu, N., Khan, N., Pillay, V., Mitchell, C. M., Dong, K. L., Ndung'u, T., Clish, C. B., Rock, C. O., Blainey, P. C., Bloom, S. M., & Kwon, D. S.
Affiliations
  • Broad Institute (US)
  • St. Jude Children's Research Hospital (US)
  • University of Kentucky (US)
  • Ragon Institute of MGH, MIT and Harvard (US)
  • Harvard University (US)
  • University of KwaZulu-Natal (ZA)
  • Health Systems Trust (ZA)
Corresponding author
  • Blainey, Paul C.
  • Bloom, Seth M.
  • Kwon, Douglas S.
Venue
Cell
Publisher
Elsevier BV
Published
2024-09
Volume
187
Issue
19
Pages
5413-5430.e29
ISSN
0092-8674 (ISSN-L)
OpenAlex
W4401698770
Cited by
61
References
112
Citations by year
2026: 27 · 2025: 29 · 2024: 5
FWCI
15.78
Type
journal article
Language
en
Open access
Locations
  • Cell (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • UKnowledge (University of Kentucky) (submittedVersion, cc-by)
Funders
  • National Science Foundation (1745302)
  • National Institute of Allergy and Infectious Diseases (5U19AI42780)
  • Bill and Melinda Gates Foundation (EC1000, 71852, 71313, 71595, 71803)
  • National Institutes of Health (1K08AI171166, 4R00AI166116)
  • Harvard University
  • St. Jude Children's Research Hospital
  • American Lebanese Syrian Associated Charities
  • Broad Institute
  • Celsius Therapeutics
Topics
  • Life Sciences › Immunology and Microbiology › Microbiology › Reproductive tract infections research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
Keywords
bacterial vaginosis, Lactobacillus crispatus, Lactobacillus iners, oleic acid, long-chain fatty acids, vaginal microbiota, bacterial fitness
MeSH terms
Lactobacillus crispatus, Anti-Bacterial Agents, Bacterial Proteins, Fatty Acids, Female, Humans, Lactobacillus, Vagina, Vaginosis, Bacterial, Oleic Acid, Microbiota

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