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Proteomic signatures of metronidazole-resistant Trichomonas vaginalis reveal novel proteins associated with drug resistance.
Parasit Vectors. 2020 Jun 01; 13(1):274.PV

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.

Authors+Show Affiliations

Division of Clinical Pathology, Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei City, 114, Taiwan.Molecular Medicine Research Center, Chang Gung University, Taoyuan City, 333, Taiwan. Liver Research Center, Chang Gung Memorial Hospital, Linkou, Taoyuan City, 333, Taiwan.Department of Biomedical Sciences, Chang Gung University, Taoyuan City, 333, Taiwan. Genomic Medicine Core Laboratory, Chang Gung Memorial Hospital, Linkou, Taoyuan City, 333, Taiwan.Molecular Regulation and Bioinformatics Laboratory, Department of Parasitology, College of Medicine, Chang Gung University, Taoyuan City, 333, Taiwan.Graduate Institute of Pathology and Parasitology, National Defense Medical Center, Taipei City, 114, Taiwan.Graduate Institute of Pathology and Parasitology, National Defense Medical Center, Taipei City, 114, Taiwan.Graduate Institute of Pathology and Parasitology, National Defense Medical Center, Taipei City, 114, Taiwan.Department of Medicine, Mackay Medical College, New Taipei City, 252, Taiwan.Division of Infection, Department of Medicine, Tri-Service General Hospital SongShan Branch, Taipei City, 105, Taiwan.Division of Family Medicine, Tri-Service General Hospital Songshan Branch, Taipei City, 105, Taiwan.Division of Clinical Pathology, Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei City, 114, Taiwan.Graduate Institute of Biomedical and Pharmaceutical Science, Fu Jen Catholic University, New Taipei City, 242, Taiwan.Molecular Regulation and Bioinformatics Laboratory, Department of Parasitology, College of Medicine, Chang Gung University, Taoyuan City, 333, Taiwan.Graduate Institute of Pathology and Parasitology, National Defense Medical Center, Taipei City, 114, Taiwan. cguhgy6934@gmail.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32487244

Citation

Lin, Hsin-Chung, et al. "Proteomic Signatures of Metronidazole-resistant Trichomonas Vaginalis Reveal Novel Proteins Associated With Drug Resistance." Parasites & Vectors, vol. 13, no. 1, 2020, p. 274.
Lin HC, Chu LJ, Huang PJ, et al. Proteomic signatures of metronidazole-resistant Trichomonas vaginalis reveal novel proteins associated with drug resistance. Parasit Vectors. 2020;13(1):274.
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. (2020). Proteomic signatures of metronidazole-resistant Trichomonas vaginalis reveal novel proteins associated with drug resistance. Parasites & Vectors, 13(1), 274. https://doi.org/10.1186/s13071-020-04148-5
Lin HC, et al. Proteomic Signatures of Metronidazole-resistant Trichomonas Vaginalis Reveal Novel Proteins Associated With Drug Resistance. Parasit Vectors. 2020 Jun 1;13(1):274. PubMed PMID: 32487244.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Proteomic signatures of metronidazole-resistant Trichomonas vaginalis reveal novel proteins associated with drug resistance. AU - Lin,Hsin-Chung, AU - Chu,Lichieh Julie, AU - Huang,Po-Jung, AU - Cheng,Wei-Hung, AU - Zheng,Yu-Hsing, AU - Huang,Ching-Yun, AU - Hong,Shu-Wen, AU - Chen,Lih-Chyang, AU - Lin,Hsin-An, AU - Wang,Jui-Yang, AU - Chen,Ruei-Min, AU - Lin,Wei-Ning, AU - Tang,Petrus, AU - Huang,Kuo-Yang, Y1 - 2020/06/01/ PY - 2020/01/30/received PY - 2020/05/25/accepted PY - 2020/6/4/entrez PY - 2020/6/4/pubmed PY - 2020/6/4/medline KW - Metronidazole resistance KW - Proteome KW - Trichomonas vaginalis SP - 274 EP - 274 JF - Parasites & vectors JO - Parasit Vectors VL - 13 IS - 1 N2 - 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. SN - 1756-3305 UR - https://www.unboundmedicine.com/medline/citation/32487244/Proteomic_signatures_of_metronidazole-resistant_Trichomonas_vaginalis_reveal_novel_proteins_associated_with_drug_resistance L2 - https://parasitesandvectors.biomedcentral.com/articles/10.1186/s13071-020-04148-5 DB - PRIME DP - Unbound Medicine ER -
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