Identification of <i>Trichomonas vaginalis</i> 5-Nitroimidazole Resistance Targets
<i>Trichomonas vaginalis</i> is the most common non-viral sexually transmitted infection. 5-nitroimidazoles are the only FDA-approved medications for <i>T. vaginalis</i> treatment. However, 5-nitroimidazole resistance has been increasingly recognized and may occur in up to 10...
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MDPI AG
2023-05-01
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| Series: | Pathogens |
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| Online Access: | https://www.mdpi.com/2076-0817/12/5/692 |
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| author | Keonte J. Graves Colin Reily Hemant K. Tiwari Vinodh Srinivasasainagendra William Evan Secor Jan Novak Christina A. Muzny |
| author_facet | Keonte J. Graves Colin Reily Hemant K. Tiwari Vinodh Srinivasasainagendra William Evan Secor Jan Novak Christina A. Muzny |
| author_sort | Keonte J. Graves |
| collection | DOAJ |
| description | <i>Trichomonas vaginalis</i> is the most common non-viral sexually transmitted infection. 5-nitroimidazoles are the only FDA-approved medications for <i>T. vaginalis</i> treatment. However, 5-nitroimidazole resistance has been increasingly recognized and may occur in up to 10% of infections. We aimed to delineate mechanisms of <i>T. vaginalis</i> resistance using transcriptome profiling of metronidazole (MTZ)-resistant and sensitive <i>T. vaginalis</i> clinical isolates. In vitro, 5-nitroimidazole susceptibility testing was performed to determine minimum lethal concentrations (MLCs) for <i>T. vaginalis</i> isolates obtained from women who had failed treatment (<i>n</i> = 4) or were successfully cured (<i>n</i> = 4). RNA sequencing, bioinformatics, and biostatistical analyses were performed to identify differentially expressed genes (DEGs) in the MTZ-resistant vs. sensitive <i>T. vaginalis</i> isolates. RNA sequencing identified 304 DEGs, 134 upregulated genes and 170 downregulated genes in the resistant isolates. Future studies with more <i>T. vaginalis</i> isolates with a broad range of MLCs are needed to determine which genes may represent the best alternative targets in drug-resistant strains. |
| first_indexed | 2024-03-11T03:25:18Z |
| format | Article |
| id | doaj.art-46b8edd1b8e145faaf14627c3344bec9 |
| institution | Directory Open Access Journal |
| issn | 2076-0817 |
| language | English |
| last_indexed | 2024-03-11T03:25:18Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pathogens |
| spelling | doaj.art-46b8edd1b8e145faaf14627c3344bec92023-11-18T02:47:00ZengMDPI AGPathogens2076-08172023-05-0112569210.3390/pathogens12050692Identification of <i>Trichomonas vaginalis</i> 5-Nitroimidazole Resistance TargetsKeonte J. Graves0Colin Reily1Hemant K. Tiwari2Vinodh Srinivasasainagendra3William Evan Secor4Jan Novak5Christina A. Muzny6Division of Infectious Diseases, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35233, USADivision of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35233, USADepartment of Biostatistics, School of Public Health, University of Alabama at Birmingham, Birmingham, AL 35233, USADepartment of Biostatistics, School of Public Health, University of Alabama at Birmingham, Birmingham, AL 35233, USADivision of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, GA 30329, USADepartment of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35233, USADivision of Infectious Diseases, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35233, USA<i>Trichomonas vaginalis</i> is the most common non-viral sexually transmitted infection. 5-nitroimidazoles are the only FDA-approved medications for <i>T. vaginalis</i> treatment. However, 5-nitroimidazole resistance has been increasingly recognized and may occur in up to 10% of infections. We aimed to delineate mechanisms of <i>T. vaginalis</i> resistance using transcriptome profiling of metronidazole (MTZ)-resistant and sensitive <i>T. vaginalis</i> clinical isolates. In vitro, 5-nitroimidazole susceptibility testing was performed to determine minimum lethal concentrations (MLCs) for <i>T. vaginalis</i> isolates obtained from women who had failed treatment (<i>n</i> = 4) or were successfully cured (<i>n</i> = 4). RNA sequencing, bioinformatics, and biostatistical analyses were performed to identify differentially expressed genes (DEGs) in the MTZ-resistant vs. sensitive <i>T. vaginalis</i> isolates. RNA sequencing identified 304 DEGs, 134 upregulated genes and 170 downregulated genes in the resistant isolates. Future studies with more <i>T. vaginalis</i> isolates with a broad range of MLCs are needed to determine which genes may represent the best alternative targets in drug-resistant strains.https://www.mdpi.com/2076-0817/12/5/692<i>Trichomonas vaginalis</i>5-nitroimidazolesresistance mechanismsdifferentially expressed genesRNA sequencing |
| spellingShingle | Keonte J. Graves Colin Reily Hemant K. Tiwari Vinodh Srinivasasainagendra William Evan Secor Jan Novak Christina A. Muzny Identification of <i>Trichomonas vaginalis</i> 5-Nitroimidazole Resistance Targets Pathogens <i>Trichomonas vaginalis</i> 5-nitroimidazoles resistance mechanisms differentially expressed genes RNA sequencing |
| title | Identification of <i>Trichomonas vaginalis</i> 5-Nitroimidazole Resistance Targets |
| title_full | Identification of <i>Trichomonas vaginalis</i> 5-Nitroimidazole Resistance Targets |
| title_fullStr | Identification of <i>Trichomonas vaginalis</i> 5-Nitroimidazole Resistance Targets |
| title_full_unstemmed | Identification of <i>Trichomonas vaginalis</i> 5-Nitroimidazole Resistance Targets |
| title_short | Identification of <i>Trichomonas vaginalis</i> 5-Nitroimidazole Resistance Targets |
| title_sort | identification of i trichomonas vaginalis i 5 nitroimidazole resistance targets |
| topic | <i>Trichomonas vaginalis</i> 5-nitroimidazoles resistance mechanisms differentially expressed genes RNA sequencing |
| url | https://www.mdpi.com/2076-0817/12/5/692 |
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