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Vaginal Lactobacillus fatty acid response mechanisms reveal a metabolite-targeted strategy for bacterial vaginosis treatment.
Zhu, Meilin; Frank, Matthew W; Radka, Christopher D; Jeanfavre, Sarah; Xu, Jiawu; Tse, Megan W; Pacheco, Julian Avila; Kim, Jae Sun; Pierce, Kerry; Deik, Amy; Hussain, Fatima Aysha; Elsherbini, Joseph; Hussain, Salina; Xulu, Nondumiso; Khan, Nasreen; Pillay, Vanessa; Mitchell, Caroline M; Dong, Krista L; Ndung'u, Thumbi; Clish, Clary B; Rock, Charles O; Blainey, Paul C; Bloom, Seth M; Kwon, Douglas S.
Affiliation
  • Zhu M; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.
  • Frank MW; Department of Host-Microbe Interactions, St. Jude Children's Research Hospital, Memphis, TN, USA.
  • Radka CD; Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky, Lexington, KY, USA.
  • Jeanfavre S; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Xu J; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.
  • Tse MW; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Pacheco JA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Kim JS; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.
  • Pierce K; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Deik A; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Hussain FA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA; Harvard Medical School, Boston, MA, USA.
  • Elsherbini J; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.
  • Hussain S; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.
  • Xulu N; HIV Pathogenesis Programme, The Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa.
  • Khan N; HIV Pathogenesis Programme, The Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa.
  • Pillay V; Health Systems Trust, Durban, South Africa.
  • Mitchell CM; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA; Harvard Medical School, Boston, MA, USA; Department of Obstetrics and Gynecology, Massachusetts General Hospital, Boston, MA, USA.
  • Dong KL; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA; Harvard Medical School, Boston, MA, USA; Health Systems Trust, Durban, South Africa; Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA.
  • Ndung'u T; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA; HIV Pathogenesis Programme, The Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa; Africa Health Research Institute, Durban, South Africa; Max Planck Institute for Infection Biology, Berlin, Germany;
  • Clish CB; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Rock CO; Department of Host-Microbe Interactions, St. Jude Children's Research Hospital, Memphis, TN, USA.
  • Blainey PC; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Koch Institute for Integrative Cancer Research at Massachusetts Institute of Technology, Cambridge, MA, USA. Electronic address: pblainey@broadinst
  • Bloom SM; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA; Harvard Medical School, Boston, MA, USA; Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA. Electronic address: smbloom@mgh.harvard.edu.
  • Kwon DS; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA; Harvard Medical School, Boston, MA, USA; Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA. Electronic address: dkwon@mgh.harvard.edu.
Cell ; 187(19): 5413-5430.e29, 2024 Sep 19.
Article in En | MEDLINE | ID: mdl-39163861
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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Full text: 1 Database: MEDLINE Main subject: Vagina / Vaginosis, Bacterial / Fatty Acids / Lactobacillus Limits: Female / Humans Language: En Journal: Cell Year: 2024 Type: Article Affiliation country: United States
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Full text: 1 Database: MEDLINE Main subject: Vagina / Vaginosis, Bacterial / Fatty Acids / Lactobacillus Limits: Female / Humans Language: En Journal: Cell Year: 2024 Type: Article Affiliation country: United States