Antimicrobial Activity of D-Form Synthetic Peptides Against Metronidazole-Resistant and Susceptible Trichomonas vaginalis: A Comparative Transcriptomic Analysis

Abstract

Trichomonas vaginalis is the causative agent of trichomoniasis, the most common non-viral sexually transmitted infection worldwide. In these cases, 5-Nitroimidazoles, particularly metronidazole (MTZ), remain the primary treatment option; however, resistance to MTZ has been increasingly reported. This study aimed to evaluate the in vitro activity of D-form synthetic antimicrobial peptides and investigate transcriptional differences associated with MTZ resistance and peptide treatment in T. vaginalis. D-form synthetic peptides (D-TN1, D-TN3, and D-TN6) developed in the R&D Laboratory of Acibadem University were tested against metronidazole-susceptible (T. vaginalis ATCC 30236) and metronidazole-resistant (T. vaginalis ATCC 50143) strains by minimum lethal concentration (MLC) assays. D-TN1 exhibited an MLC of 16 & micro;g/mL in both strains, whereas D-TN3 and D-TN6 exhibited MLC values of 32 & micro;g/mL and 16-32 & micro;g/mL, respectively. Comparative transcriptomic analysis was conducted to investigate transcriptional differences. Differential gene expression analysis identified 3395 genes between the resistant and susceptible isolates and 3060 genes in the D-TN1-treated resistant isolate (FDR < 0.05, |log(2)FC| >= 1). D-TN1 treatment in the resistant isolate was associated with downregulation of ribosomal and metabolic pathways. If confirmed with further in vivo studies, this new antimicrobial peptide may become a new therapeutic alternative in the treatment of trichomoniasis in the future.