Pathogens (May 2023)

Identification of <i>Trichomonas vaginalis</i> 5-Nitroimidazole Resistance Targets

  • Keonte J. Graves,
  • Colin Reily,
  • Hemant K. Tiwari,
  • Vinodh Srinivasasainagendra,
  • William Evan Secor,
  • Jan Novak,
  • Christina A. Muzny

DOI
https://doi.org/10.3390/pathogens12050692
Journal volume & issue
Vol. 12, no. 5
p. 692

Abstract

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Trichomonas vaginalis is the most common non-viral sexually transmitted infection. 5-nitroimidazoles are the only FDA-approved medications for T. vaginalis treatment. However, 5-nitroimidazole resistance has been increasingly recognized and may occur in up to 10% of infections. We aimed to delineate mechanisms of T. vaginalis resistance using transcriptome profiling of metronidazole (MTZ)-resistant and sensitive T. vaginalis clinical isolates. In vitro, 5-nitroimidazole susceptibility testing was performed to determine minimum lethal concentrations (MLCs) for T. vaginalis isolates obtained from women who had failed treatment (n = 4) or were successfully cured (n = 4). RNA sequencing, bioinformatics, and biostatistical analyses were performed to identify differentially expressed genes (DEGs) in the MTZ-resistant vs. sensitive T. vaginalis isolates. RNA sequencing identified 304 DEGs, 134 upregulated genes and 170 downregulated genes in the resistant isolates. Future studies with more T. vaginalis isolates with a broad range of MLCs are needed to determine which genes may represent the best alternative targets in drug-resistant strains.

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