Cysteine dependence of Lactobacillus iners is a potential therapeutic target for vaginal microbiota modulation.
Journal
Nature microbiology
ISSN: 2058-5276
Titre abrégé: Nat Microbiol
Pays: England
ID NLM: 101674869
Informations de publication
Date de publication:
03 2022
03 2022
Historique:
received:
16
06
2021
accepted:
27
01
2022
entrez:
4
3
2022
pubmed:
5
3
2022
medline:
20
4
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 35241796
doi: 10.1038/s41564-022-01070-7
pii: 10.1038/s41564-022-01070-7
pmc: PMC10473153
mid: NIHMS1775954
doi:
Substances chimiques
Metronidazole
140QMO216E
Cysteine
K848JZ4886
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
434-450Subventions
Organisme : NIAID NIH HHS
ID : P30 AI060354
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI111918
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI007387
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer Nature Limited.
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