Journal article
Metronidazole response profiles of Gardnerella species are congruent with phylogenetic and comparative genomic analyses
Genome medicine, v 17(1), 28
25 Mar 2025
PMID: 40133961
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
<p>Background Bacterial 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 mu g/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 mu g/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.</p>
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Details
- Title
- Metronidazole response profiles of Gardnerella species are congruent with phylogenetic and comparative genomic analyses
- Creators
- Katherine A. Innamorati - Drexel UniversityJoshua P. Earl - Drexel UniversityShirley C. Barrera - Drexel UniversityRachel L. Ehrlich - Drexel UniversityJosephine Aiyeku - Drexel UniversityAri Gordon - Philadelphia, PA USA Philadelphia, PA USA 245 N 15th St, Rm 5110, Philadelphia, PA USAEvan Powell - Magee-Womens HospitalAdam C. Retchless - Allegheny-Singer Research InstituteAzad Ahmed - Drexel UniversityBhaswati Sen - Drexel UniversitySergey Balashov - Drexel UniversityJoshua Chang Mell - Drexel UniversitySharon L. Hillier - University of PittsburghGarth D. Ehrlich - Drexel University
- Publication Details
- Genome medicine, v 17(1), 28
- Publisher
- BioMed Central
- Number of pages
- 18
- Grant note
- Funds from the Institute of Molecular Medicine and Infectious Diseases at Drexel UniversityMary Dewitt Pettit, MD FellowshipOskar Fischer Project (a James Truchard Philanthropy)Bill and Marian Cook FoundationNIH: DC01428, DK082316
This work was supported by funds from the Institute of Molecular Medicine and Infectious Diseases at Drexel University and the Mary Dewitt Pettit, MD Fellowship. Additional funding was provided by the Oskar Fischer Project (a James Truchard Philanthropy), the Bill and Marian Cook Foundation, and NIH grants DC01428 and DK082316.
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology; College of Medicine
- Web of Science ID
- WOS:001451495900001
- Scopus ID
- 2-s2.0-105000727071
- Other Identifier
- 991022041973304721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Genetics & Heredity