2020
Lin, H. -C.; Chu, L. J.; Huang, P. -J.; Cheng, W. -H.; Zheng, Y. -H.; Huang, C. -Y.; Hong, S. -W.; Chen, L. -C.; Lin, H. -A.; Wang, J. -Y.; Chen, R. -M.; Lin, W. -N.; Tang, P.; Huang, K. -Y.
Proteomic signatures of metronidazole-resistant Trichomonas vaginalis reveal novel proteins associated with drug resistance Journal Article
In: Parasites and Vectors, 13 (1), 2020, ISSN: 17563305, (cited By 1).
Abstract | Links | BibTeX | 標籤: alanine; arginine; aspartic acid; bafilomycin A1; glutamic acid; hydrolase; metronidazole; oligomycin; proline; proteome; proton transporting adenosine triphosphate synthase; antiprotozoal agent; metronidazole; protozoal protein, Antiprotozoal Agents; Down-Regulation; Drug Resistance; Mass Spectrometry; Metronidazole; Protein Interaction Maps; Proteomics; Protozoan Proteins; Trichomonas vaginalis; Up-Regulation
@article{Lin2020,
title = {Proteomic signatures of metronidazole-resistant Trichomonas vaginalis reveal novel proteins associated with drug resistance},
author = {H. -C. Lin and L. J. Chu and P. -J. Huang and W. -H. Cheng and Y. -H. Zheng and C. -Y. Huang and S. -W. Hong and L. -C. Chen and H. -A. Lin and J. -Y. Wang and R. -M. Chen and W. -N. Lin and P. Tang and K. -Y. Huang},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85085910154&doi=10.1186%2fs13071-020-04148-5&partnerID=40&md5=146613f2c297776c7c895d308dd2cfe0},
doi = {10.1186/s13071-020-04148-5},
issn = {17563305},
year = {2020},
date = {2020-01-01},
journal = {Parasites and Vectors},
volume = {13},
number = {1},
publisher = {BioMed Central},
abstract = {Background: Trichomoniasis is the most common non-viral sexually transmitted disease caused by the protozoan parasite Trichomonas vaginalis. Metronidazole (MTZ) is a widely used drug for the treatment of trichomoniasis; however, increased resistance of the parasite to MTZ has emerged as a highly problematic public health issue. Methods: We conducted iTRAQ-based analysis to profile the proteomes of MTZ-sensitive (MTZ-S) and MTZ-resistant (MTZ-R) parasites. STRING and gene set enrichment analysis (GESA) were utilized to explore the protein-protein interaction networks and enriched pathways of the differentially expressed proteins, respectively. Proteins potentially related to MTZ resistance were selected for functional validation. Results: A total of 3123 proteins were identified from the MTZ-S and MTZ-R proteomes in response to drug treatment. Among the identified proteins, 304 proteins were differentially expressed in the MTZ-R proteome, including 228 upregulated and 76 downregulated proteins. GSEA showed that the amino acid-related metabolism, including arginine, proline, alanine, aspartate, and glutamate are the most upregulated pathways in the MTZ-R proteome, whereas oxidative phosphorylation is the most downregulated pathway. Ten proteins categorized into the gene set of oxidative phosphorylation were ATP synthase subunit-related proteins. Drug resistance was further examined in MTZ-S parasites pretreated with the ATP synthase inhibitors oligomycin and bafilomycin A1, showing enhanced MTZ resistance and potential roles of ATP synthase in drug susceptibility. Conclusions: We provide novel insights into previously unidentified proteins associated with MTZ resistance, paving the way for future development of new drugs against MTZ-refractory trichomoniasis. © 2020 The Author(s).},
note = {cited By 1},
keywords = {alanine; arginine; aspartic acid; bafilomycin A1; glutamic acid; hydrolase; metronidazole; oligomycin; proline; proteome; proton transporting adenosine triphosphate synthase; antiprotozoal agent; metronidazole; protozoal protein, Antiprotozoal Agents; Down-Regulation; Drug Resistance; Mass Spectrometry; Metronidazole; Protein Interaction Maps; Proteomics; Protozoan Proteins; Trichomonas vaginalis; Up-Regulation},
pubstate = {published},
tppubtype = {article}
}
Background: Trichomoniasis is the most common non-viral sexually transmitted disease caused by the protozoan parasite Trichomonas vaginalis. Metronidazole (MTZ) is a widely used drug for the treatment of trichomoniasis; however, increased resistance of the parasite to MTZ has emerged as a highly problematic public health issue. Methods: We conducted iTRAQ-based analysis to profile the proteomes of MTZ-sensitive (MTZ-S) and MTZ-resistant (MTZ-R) parasites. STRING and gene set enrichment analysis (GESA) were utilized to explore the protein-protein interaction networks and enriched pathways of the differentially expressed proteins, respectively. Proteins potentially related to MTZ resistance were selected for functional validation. Results: A total of 3123 proteins were identified from the MTZ-S and MTZ-R proteomes in response to drug treatment. Among the identified proteins, 304 proteins were differentially expressed in the MTZ-R proteome, including 228 upregulated and 76 downregulated proteins. GSEA showed that the amino acid-related metabolism, including arginine, proline, alanine, aspartate, and glutamate are the most upregulated pathways in the MTZ-R proteome, whereas oxidative phosphorylation is the most downregulated pathway. Ten proteins categorized into the gene set of oxidative phosphorylation were ATP synthase subunit-related proteins. Drug resistance was further examined in MTZ-S parasites pretreated with the ATP synthase inhibitors oligomycin and bafilomycin A1, showing enhanced MTZ resistance and potential roles of ATP synthase in drug susceptibility. Conclusions: We provide novel insights into previously unidentified proteins associated with MTZ resistance, paving the way for future development of new drugs against MTZ-refractory trichomoniasis. © 2020 The Author(s).