Vaginal Lactobacillus fatty acid response mechanisms reveal a novel strategy for bacterial vaginosis treatment.

Autor:	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, Tennessee, USA., Radka CD; Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky., Jeanfavre S; Broad Institute of 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., Pierce K; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Deik A; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Xu J; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA., Hussain S; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA., Hussain FA; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.; Harvard Medical School, Boston, MA, USA., Xulu N; HIV Pathogenesis Programme (HPP), The Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa., Khan N; HIV Pathogenesis Programme (HPP), The Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa., Pillay V; Health Systems Trust, Durban, South Africa., Dong KL; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.; Health Systems Trust, Durban, South Africa.; Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA.; Harvard Medical School, Boston, MA, USA., Ndung'u T; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.; HIV Pathogenesis Programme (HPP), The Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa.; Africa Health Research Institute (AHRI), Durban, South Africa.; Max Planck Institute for Infection Biology, Berlin, Germany.; Division of Infection and Immunity, University College London, London, UK., 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, Tennessee, USA.; passed away on September 22, 2023., 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., Bloom SM; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.; Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA.; Harvard Medical School, Boston, MA, USA., Kwon DS; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.; Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA.; Harvard Medical School, Boston, MA, USA.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2023 Dec 30. Date of Electronic Publication: 2023 Dec 30.
DOI:	10.1101/2023.12.30.573720
Abstrakt:	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 species, including an oleate hydratase ( ohyA ) and putative fatty acid efflux pump ( farE ). FarE mediates OA resistance, while OhyA is robustly active in the human vaginal microbiota and sequesters OA in a derivative form that only ohyA -harboring organisms can exploit. Finally, OA promotes L. crispatus dominance more effectively than antibiotics in an in vitro model of BV, suggesting a novel approach for treatment. Competing Interests: Conflicts of Interests M.Z., S.M.B., P.C.B., and D.S.K. are co-inventors on a patent related to this work. P.C.B is a co-inventor on patent applications concerning droplet array technologies and serves as a consultant and equity holder of companies in the microfluidics and life sciences industries, including 10x Genomics, GALT/Isolation Bio, Celsius Therapeutics, Next Gen Diagnostics, Cache DNA, Concerto Biosciences, Amber Bio, Stately, Ramona Optics, and Bifrost Biosystems. D.S.K. serves as equity holder of Day Zero Diagnostics.
Databáze:	MEDLINE
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