Novel insights into the molecular events linking to cell death induced by tetracycline in the amitochondriate protozoan Trichomonas vaginalis

Kuo Yang Huang, Fu Man Ku, Wei Hung Cheng, Chi Ching Lee, Po Jung Huang, Lichieh Julie Chu, Chih Chieh Cheng, Yi Kai Fang, Hsueh Hsia Wu, Petrus Tang

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Trichomonas vaginalis colonizes the human urogenital tract and causes trichomoniasis, the most common nonviral sexually transmitted disease. Currently, 5-nitroimidazoles are the only recommended drugs for treating trichomoniasis. However, increased resistance of the parasite to 5-nitroimidazoles has emerged as a highly problematic public health issue. Hence, it is essential to identify alternative chemotherapeutic agents against refractory trichomoniasis. Tetracycline (TET) is a broad-spectrum antibiotic with activity against several protozoan parasites, but the mode of action of TET in parasites remains poorly understood. The in vitro effect of TET on the growth of T. vaginalis was examined, and the mode of cell death was verified by various apoptosis-related assays. Next-generation sequencing-based RNA sequencing (RNA-seq) was employed to elucidate the transcriptome of T. vaginalis in response to TET. We show that TET has a cytotoxic effect on both metronidazole (MTZ)-sensitive and - resistant T. vaginalis isolates, inducing some features resembling apoptosis. RNA-seq data reveal that TET significantly alters the transcriptome via activation of specific pathways, such as aminoacyl-tRNA synthetases and carbohydrate metabolism. Functional analyses demonstrate that TET disrupts the hydrogenosomal membrane potential and antioxidant system, which concomitantly elicits a metabolic shift toward glycolysis, suggesting that the hydrogenosomal function is impaired and triggers cell death. Collectively, we provide in vitro evidence that TET is a potential alternative therapeutic choice for treating MTZ-resistant T. vaginalis. The in-depth transcriptomic signatures in T. vaginalis upon TET treatment presented here will shed light on the signaling pathways linking to cell death in amitochondriate organisms.

Original languageEnglish
Pages (from-to)6891-6903
Number of pages13
JournalAntimicrobial Agents and Chemotherapy
Volume59
Issue number11
DOIs
Publication statusPublished - Nov 1 2015

Fingerprint

Trichomonas vaginalis
Tetracycline
Cell Death
RNA Sequence Analysis
Parasites
Metronidazole
Transcriptome
Apoptosis
Amino Acyl-tRNA Synthetases
Carbohydrate Metabolism
Glycolysis
Sexually Transmitted Diseases
Membrane Potentials
Public Health
Antioxidants
Anti-Bacterial Agents

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology
  • Infectious Diseases

Cite this

Novel insights into the molecular events linking to cell death induced by tetracycline in the amitochondriate protozoan Trichomonas vaginalis. / Huang, Kuo Yang; Ku, Fu Man; Cheng, Wei Hung; Lee, Chi Ching; Huang, Po Jung; Chu, Lichieh Julie; Cheng, Chih Chieh; Fang, Yi Kai; Wu, Hsueh Hsia; Tang, Petrus.

In: Antimicrobial Agents and Chemotherapy, Vol. 59, No. 11, 01.11.2015, p. 6891-6903.

Research output: Contribution to journalArticle

Huang, Kuo Yang ; Ku, Fu Man ; Cheng, Wei Hung ; Lee, Chi Ching ; Huang, Po Jung ; Chu, Lichieh Julie ; Cheng, Chih Chieh ; Fang, Yi Kai ; Wu, Hsueh Hsia ; Tang, Petrus. / Novel insights into the molecular events linking to cell death induced by tetracycline in the amitochondriate protozoan Trichomonas vaginalis. In: Antimicrobial Agents and Chemotherapy. 2015 ; Vol. 59, No. 11. pp. 6891-6903.
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