Evidence map›Paper›PMID 40133961›Full record

ArticleGenome medicine2025

Metronidazole response profiles of Gardnerella species are congruent with phylogenetic and comparative genomic analyses.

Katherine A Innamorati, Joshua P Earl, Shirley C Barrera, Rachel L Ehrlich, Josephine Aiyeku, Ari Gordon, Evan Powell, Adam C Retchless, Azad Ahmed, Bhaswati Sen and 4 more

Abstract read
In one paragraph

Article in Genome medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
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

4 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Strain-level differences inbioRxiv : the preprint server for biology · 2025
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Katherine A InnamoratiCenter for Advanced Microbial Processing, Drexel University College of Medicine, Philadelphia, PA, USA.
Joshua P EarlCenter for Advanced Microbial Processing, Drexel University College of Medicine, Philadelphia, PA, USA. jpe39@dragons.drexel.edu.
Shirley C BarreraDepartment of Microbiology and Immunology, Drexel University College of Medicine, 245 N 15th St, Rm 5110, Philadelphia, PA, USA.
Rachel L EhrlichCenter for Advanced Microbial Processing, Drexel University College of Medicine, Philadelphia, PA, USA.
Josephine AiyekuCenter for Advanced Microbial Processing, Drexel University College of Medicine, Philadelphia, PA, USA.
Ari GordonCenter for Advanced Microbial Processing, Drexel University College of Medicine, Philadelphia, PA, USA.
Evan PowellMagee-Women's Hospital of University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
Adam C RetchlessCenter for Genomic Sciences, Allegheny Singer Research Institute, Pittsburgh, PA, USA.
Azad AhmedCenter for Advanced Microbial Processing, Drexel University College of Medicine, Philadelphia, PA, USA.
Bhaswati SenCenter for Advanced Microbial Processing, Drexel University College of Medicine, Philadelphia, PA, USA.
Sergey BalashovCenter for Advanced Microbial Processing, Drexel University College of Medicine, Philadelphia, PA, USA.
Joshua Chang MellCenter for Advanced Microbial Processing, Drexel University College of Medicine, Philadelphia, PA, USA.
Sharon L HillierUniversity of Pittsburgh, Pittsburgh, PA, USA.
Garth D EhrlichCenter for Advanced Microbial Processing, Drexel University College of Medicine, Philadelphia, PA, USA. ge33@drexel.edu.ORCID 0000-0003-0341-8771

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundBacterial vaginosis (BV) affects 20-50% of reproductive-age female patients annually, arising when opportunistic pathogens outcompete healthy vaginal flora. Many patients fail to resolve symptoms with a course of metronidazole, the current first-line treatment for BV. Our study was designed to identify genomic variation associated with metronidazole resistance among strains of Gardnerella vaginalis spp. (GV), a genus of biogenic-amine-producing bacteria closely associated with BV pathogenesis, for the development of a companion molecular diagnostic.

methodsWhole-genome sequencing and comparative genomic metrics, including average nucleotide identity and GC content, were performed on a diverse set of 129 GV genomes to generate data for detailed taxonomic analyses. Pangenomic analyses were employed to construct a phylogenetic tree and cluster highly related strains within genospecies. G. vaginalis spp. clinical isolates within our collection were subjected to plate-based minimum inhibitory concentration (MIC) testing of metronidazole (n = 60) and clindamycin (n = 63). DECIPHER and MAFFT were used to identify genospecies-specific primers associated with antibiotic-resistance phenotypes. PCR-based analyses with these primers were used to confirm their specificity for the relevant genospecies.

resultsEleven distinct genospecies based on standard ANI criteria were identified among the GV strains in our collection. Metronidazole MIC testing revealed six genospecies within a closely related phylogenetic clade contained only highly metronidazole-resistant strains (MIC ≥ 32 µg/mL) and suggested at least two mechanisms of metronidazole resistance within the eleven GV genospecies. All strains within the six highly metronidazole-resistant genospecies displayed susceptibility to clinically relevant clindamycin concentrations (MIC ≤ 2 µg/mL). A PCR-based molecular diagnostic assay was developed to distinguish between members of the metronidazole-resistant and mixed-response genospecies, which should be useful for determining the clade membership of various GV strains and could assist in the selection of appropriate antibiotic therapies for BV cases.

conclusionsThis study provides comparative genomic and phylogenetic evidence for eleven distinct genospecies within the genus Gardnerella vaginalis spp., and identifies genospecies-specific responses to metronidazole, the first-line treatment for BV. A companion molecular diagnostic assay was developed that is capable of identifying essentially all highly metronidazole-resistant strains that phylogenetically cluster together within the GV genospecies, which is informative for antibiotic treatment options.

Indexed as

Anti-Bacterial AgentsGardnerella vaginalisGenome, BacterialGenomicsMetronidazolePhylogenyDrug Resistance, BacterialFemaleHumansMicrobial Sensitivity TestsVaginosis, BacterialWhole Genome SequencingAnti-Bacterial AgentsMetronidazoleAntibiotic resistanceBacterial vaginosisComparative genomicsDistributed genome hypothesisGardnerella vaginalisMetronidazole resistanceMolecular diagnosticPangenomePhylogeneticsSupragenome

Identifiers

PMID40133961
PMCPMC11934483

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LicenceCC BY-NC-ND
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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.