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Antimicrobial Activity of D-Form Synthetic Peptides Against Metronidazole-Resistant and Susceptible Trichomonas

Özben Özden1, Tuba Polat1, Tanıl Kocagöz1,2

  • 1Graduate School of Health Sciences, Department of Medical Biotechnology, Acibadem University, Istanbul 34752, Türkiye.

International Journal of Molecular Sciences
|May 13, 2026
PubMed

Insights

New antimicrobial peptides show promise against metronidazole-resistant Trichomonas vaginalis, the cause of trichomoniasis. D-TN1 peptide effectively killed both susceptible and resistant strains in vitro, suggesting a potential new treatment for this common STI.

Area of Science:

  • Antimicrobial Peptides
  • Parasitic Infections
  • Drug Resistance

Background:

  • Trichomoniasis, caused by *Trichomonas vaginalis*, is the most common non-viral sexually transmitted infection globally.
  • Metronidazole (MTZ) is the primary treatment, but MTZ resistance in *T. vaginalis* is a growing concern.
  • Novel therapeutic strategies are needed to combat resistant strains of *T. vaginalis*.

Purpose of the Study:

  • To evaluate the in vitro antimicrobial activity of D-form synthetic peptides against *T. vaginalis*.
  • To investigate transcriptional changes associated with MTZ resistance and peptide treatment in *T. vaginalis*.
  • To identify potential new therapeutic alternatives for trichomoniasis.

Main Methods:

  • Minimum Lethal Concentration (MLC) assays were performed using D-form synthetic peptides (D-TN1, D-TN3, D-TN6) against MTZ-susceptible and MTZ-resistant *T. vaginalis* strains.
  • Comparative transcriptomic analysis was conducted on MTZ-resistant and susceptible isolates.
  • Differential gene expression analysis was performed on MTZ-resistant isolates before and after D-TN1 treatment.

Main Results:

  • D-TN1 demonstrated potent in vitro activity with an MLC of 16 µg/mL against both MTZ-susceptible and MTZ-resistant *T. vaginalis* strains.
  • Differential gene expression analysis revealed significant transcriptional differences between resistant and susceptible isolates (3395 genes).
  • D-TN1 treatment in resistant isolates led to the downregulation of ribosomal and metabolic pathways (3060 genes).

Conclusions:

  • D-form synthetic antimicrobial peptides, particularly D-TN1, exhibit significant in vitro efficacy against *T. vaginalis*, including MTZ-resistant strains.
  • Transcriptomic analysis provides insights into the molecular mechanisms underlying MTZ resistance and peptide action.
  • D-TN1 represents a promising candidate for a novel therapeutic agent against trichomoniasis, warranting further in vivo investigation.
Keywords:
Trichomonas vaginalisantimicrobial peptidesdrug resistancemetronidazoletranscriptome

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