Proteomic signatures of metronidazole-resistant Trichomonas vaginalis reveal novel proteins associated with drug resistance.
Parasit Vectors
; 13(1): 274, 2020 Jun 01.
Article
em En
| MEDLINE
| ID: mdl-32487244
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Trichomonas vaginalis
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Resistência a Medicamentos
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Proteínas de Protozoários
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Metronidazol
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Antiprotozoários
Tipo de estudo:
Risk_factors_studies
Idioma:
En
Revista:
Parasit Vectors
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Taiwan
País de publicação:
ENGLAND
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ESCOCIA
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GB
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GREAT BRITAIN
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INGLATERRA
/
REINO UNIDO
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SCOTLAND
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UK
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UNITED KINGDOM