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

Authors :
Huang KY
Ku FM
Cheng WH
Lee CC
Huang PJ
Chu LJ
Cheng CC
Fang YK
Wu HH
Tang P
Source :
Antimicrobial agents and chemotherapy [Antimicrob Agents Chemother] 2015 Nov; Vol. 59 (11), pp. 6891-903. Date of Electronic Publication: 2015 Aug 24.
Publication Year :
2015

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.<br /> (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

Details

Language :
English
ISSN :
1098-6596
Volume :
59
Issue :
11
Database :
MEDLINE
Journal :
Antimicrobial agents and chemotherapy
Publication Type :
Academic Journal
Accession number :
26303799
Full Text :
https://doi.org/10.1128/AAC.01779-15