Evidence map›Paper›PMID 35241796›Full record

ArticleNature microbiology2022

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

Seth M Bloom, Nomfuneko A Mafunda, Benjamin M Woolston, Matthew R Hayward, Josephine F Frempong, Aaron B Abai, Jiawu Xu, Alissa J Mitchell, Xavier Westergaard, Fatima A Hussain and 14 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature microbiology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.

0numbers the graph read from it
0cells of the map it votes in
78citing papers in PubMed
13.3field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

78 citing papers in PubMed, 107 citations in OpenAlex.

  1. Trial
  2. Trial
  3. Vaginal formulations selectively target Lactobacillus iners and Candida spp. while preserving Lactobacillus crispatus.International microbiology : the official journal of the Spanish Society for Microbiology · 2026
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  10. Nutrient control enables metabolic reconstruction ofbioRxiv : the preprint server for biology · 2026
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18 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

24 authors at 10 institutions in 4 countries.

Seth M BloomRagon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-0462-4596
Nomfuneko A MafundaRagon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
Benjamin M WoolstonDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-6570-2236
Matthew R HaywardRagon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
Josephine F FrempongRagon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
Aaron B AbaiHarvard College, Harvard University, Cambridge, MA, USA.
Jiawu XuRagon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
Alissa J MitchellDepartment of Obstetrics and Gynecology, Massachusetts General Hospital, Boston, MA, USA.
Xavier WestergaardRagon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
Fatima A HussainRagon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-8926-3875
Nondumiso XuluHIV Pathogenesis Programme (HPP), The Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa.
Mary DongRagon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
Krista L DongRagon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-2038-3518
Thandeka GumbiHealth Systems Trust, Durban, South Africa.
F Xolisile CeasarHealth Systems Trust, Durban, South Africa.
Justin K RiceHarvard Medical School, Boston, MA, USA.
Namit ChoksiDepartment of Obstetrics and Gynecology, Massachusetts General Hospital, Boston, MA, USA.
Nasreen IsmailHIV Pathogenesis Programme (HPP), The Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa.
Thumbi Ndung'uRagon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
Musie S GhebremichaelRagon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
David A RelmanDepartment of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.ORCID http://orcid.org/0000-0001-8331-1354
Emily P BalskusDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-5985-5714
Caroline M MitchellRagon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-9924-2349
Douglas S KwonRagon Institute of MGH, MIT and Harvard, Cambridge, MA, USA. dkwon@mgh.harvard.edu.ORCID http://orcid.org/0000-0001-8521-8735
Harvard University · USRagon Institute of MGH, MIT and Harvard · USHealth Systems Trust · ZAUniversity of KwaZulu-Natal · ZAHarvard University Press · USMassachusetts General Hospital · USNortheastern University · USVA Palo Alto Health Care System · USWashington University in St. Louis · USWilliam Carey University · US

Funding

The impact of HIV viral diversity and cellular immunity on HIV pathogenesisP30AI060354 · NIAID · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI RAJESH T GANDHI · 2004 to 2026
$94.4M
RP5: Chemical proteomic discovery of small-molecule probes for autophagy proteinsU19AI142784 · NIAID · UT SOUTHWESTERN MEDICAL CENTER · PI VIRGIN, HERBERT W · 2019 to 2023
$36.9M
Multidisciplinary HIV Training ProgramT32AI007387 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI Daniel R. Kuritzkes · 1990 to 2026
$8.8M
Inflammation and the vaginal metagenome in HIV acquisitionR01AI111918 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI KWON, DOUGLAS, VIRGIN, HERBERT W · 2014 to 2017
$2.5M
NIAID NIH HHS P30 AI060354NIAID NIH HHS R01 AI111918NIAID NIH HHS T32 AI007387NIAID NIH HHS U19 AI142784
6 · The paper itself

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.

Indexed as

MicrobiotaVaginosis, BacterialCysteineFemaleHumansLactobacillusMetronidazoleVaginaCysteineMetronidazole

Identifiers

PMID35241796
PMCPMC10473153
OpenAlexW4214823714

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.