The following is a summary of “Identification of trichomonas vaginalis 5-nitroimidazole resistance targets to inform future drug development,” published in the FEBRUARY 2023 issue of Obstetrics and Gynecology by Graves K, et al.

For a study, researchers sought to understand the mechanisms of resistance to 5-nitroimidazoles (metronidazole [MTZ], tinidazole [TIN], and secnidazole [SEC]) in T. vaginalis by analyzing the transcriptome of MTZ-resistant and MTZ-sensitive isolates.

The study used T. vaginalis isolates, four MTZ-resistant (minimal lethal concentration (MLC) ≥50μg/ml) and four MTZ-sensitive (MLC ≤25μg/ml). The isolates were grown in Diamond’s Trypticase-Yeast-Maltose medium and underwent 5-nitroimidazole susceptibility testing to confirm MLCs. Total RNA extraction was done using Trizol reagent, followed by RNA sequencing (RNAseq) and bioinformatics analysis to identify differentially expressed genes (DEGs) in MTZ-resistant and MTZ-sensitive isolates.

RNAseq analysis identified multiple DEGs in MTZ-resistant isolates compared to MTZ-sensitive isolates. The DEGs in MTZ-resistant isolates were associated with metabolic pathways, such as energy/carbohydrate metabolism, detoxification, and oxygen scavenging, relevant to 5-nitroimidazole resistance. Other DEGs included genes encoding transcription factors (MYB DNA-binding protein), ribosomal proteins, protein kinases, ankyrin-repeat proteins, surface proteins, and several uncharacterized conserved hypothetical proteins.

The study identified several DEGs in MTZ-resistant T. vaginalis isolates, including genes involved in downregulated protein synthesis and surface proteins upregulated. The upregulation of surface proteins in MTZ-resistant isolates suggests increased expression of certain virulence factors. Further studies with larger numbers of isolates representing a broader range of 5-nitroimidazole-susceptibility patterns are necessary to identify new targets for future drug development.

Reference: ajog.org/article/S0002-9378(22)01003-1/fulltext