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Cysteine dependence of Lactobacillus iners is a potential therapeutic target for vaginal microbiota modulation

Bloom, SM; Mafunda, NA; Woolston, BM; Hayward, MR; Frempong, JF; Abai, AB; Xu, J; ... Kwon, DS; + view all (2022) Cysteine dependence of Lactobacillus iners is a potential therapeutic target for vaginal microbiota modulation. Nature Microbiology , 7 pp. 434-450. 10.1038/s41564-022-01070-7. Green open access

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Abstract

Vaginal microbiota composition affects many facets of reproductive health. Lactobacillus iners-dominated microbial communities are associated with poorer outcomes, including higher risk of bacterial vaginosis (BV), compared with vaginal microbiota rich in L. crispatus. Unfortunately, standard-of-care metronidazole therapy for BV typically results in dominance of L. iners, probably contributing to post-treatment relapse. Here we generate an L. iners isolate collection comprising 34 previously unreported isolates from 14 South African women with and without BV and 4 previously unreported isolates from 3 US women. We also report an associated genome catalogue comprising 1,218 vaginal Lactobacillus isolate genomes and metagenome-assembled genomes from >300 women across 4 continents. We show that, unlike L. crispatus, L. iners growth is dependent on L-cysteine in vitro and we trace this phenotype to the absence of canonical cysteine biosynthesis pathways and a restricted repertoire of cysteine-related transport mechanisms. We further show that cysteine concentrations in cervicovaginal lavage samples correlate with Lactobacillus abundance in vivo and that cystine uptake inhibitors selectively inhibit L. iners growth in vitro. Combining an inhibitor with metronidazole promotes L. crispatus dominance of defined BV-like communities in vitro by suppressing L. iners growth. Our findings enable a better understanding of L. iners biology and suggest candidate treatments to modulate the vaginal microbiota to improve reproductive health for women globally.

Type: Article
Title: Cysteine dependence of Lactobacillus iners is a potential therapeutic target for vaginal microbiota modulation
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s41564-022-01070-7
Publisher version: https://doi.org/10.1038/s41564-022-01070-7
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Science & Technology, Life Sciences & Biomedicine, Microbiology, BACTERIAL VAGINOSIS, HIV ACQUISITION, WOMEN, RECURRENCE, RISK
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL
URI: https://discovery.ucl.ac.uk/id/eprint/10156884
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