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208 Identification of Trichomonas vaginalis 5-nitroimidazole resistance targets to inform future drug development

Published online by Cambridge University Press:  19 April 2022

Keonte Graves ,
Jyoti Sharma ,
Colin Reily ,
Hemant Tiwari ,
Vinodh Srinivasasainagendra ,
W. Evan Secor ,
Jan Novak  and
Christina A. Muzny
Keonte Graves
Affiliation:
CCTS
Jyoti Sharma
Affiliation:
Department of Microbiology, The University of Alabama at Birmingham
Colin Reily
Affiliation:
Department of Medicine, The University of Alabama at Birmingham Department of Microbiology, The University of Alabama at Birmingham
Hemant Tiwari
Affiliation:
Department of Biostatistics, The University of Alabama at Birmingham
Vinodh Srinivasasainagendra
Affiliation:
Department of Biostatistics, The University of Alabama at Birmingham
W. Evan Secor
Affiliation:
Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention
Jan Novak
Affiliation:
Department of Microbiology, The University of Alabama at Birmingham
Christina A. Muzny
Affiliation:
Department of Medicine, The University of Alabama at Birmingham
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Abstract

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OBJECTIVES/GOALS: 5-nitroimidazoles are the only FDA-approved medications for T. vaginalis treatment. Resistance has been observed in 5-10% of cases, but may be rising. We aimed to delineate mechanisms of resistance in isolates of T. vaginalis using transcriptome profiling of resistant and sensitive T. vaginalis isolates. METHODS/STUDY POPULATION: T. vaginalis isolates (4 metronidazole (MTZ)-resistant were grown in triplicate in Diamond’s Trypticase-Yeast-Maltose medium. MTZ susceptibility testing confirmed MTZ MLCs of T. vaginalis isolates. Total RNA extraction was done using Trizol reagent (Invitrogen; Carlsbad; CA); according to the manufacturer’s instructions. RNA sequencing (RNAseq) and bioinformatics analyses were performed to identify significantly differentially expressed genes (DEGs) in MTZ-resistant vs. sensitive isolates. Subsequent qPCR was performed to confirm and extend RNAseq data and gene targets related to 5-nitroimidazole resistance. RESULTS/ANTICIPATED RESULTS: RNAseq identified key DEGs in MTZ-resistant vs. sensitive isolates. DEGs from MTZ-resistant isolates included those involved in metabolic pathways relevant to 5-nitroimidazole resistance such as energy production (glycolytic enzymes) and oxygen-scavenging (thioredoxin). Other DEGs included those encoding transcription factors (MYB DNA-binding protein), ribosomal proteins (30S, 40S, 50S, 60S), protein kinases (CAMK, ser/thr, CMGC), Ankyrin repeat proteins, surface proteins (Surface antigen BspA-like) and various uncharacterized hypothetical proteins. RT-qPCR experiments confirmed reduced expression of genes encoding ferredoxin (drug activation) and flavin reductase 1 (oxygen scavenging) in MTZ-resistant T. vaginalis isolates as compared to MTZ-sensitive isolates. DISCUSSION/SIGNIFICANCE: In this study, we identified several DEGs in resistant T. vaginalis isolates. Further studies with large number of isolates representing a broad range of MTZ-susceptibility patterns are needed to identify genes that may represent new targets for future drug development.

Type
Education
Information
Journal of Clinical and Translational Science , Volume 6 , Issue s1 , April 2022 , pp. 32
Creative Commons
Creative Common License - CCCreative Common License - BYCreative Common License - NCCreative Common License - ND
This is an Open Access article, distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives licence (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is unaltered and is properly cited. The written permission of Cambridge University Press must be obtained for commercial re-use or in order to create a derivative work.
Copyright
© The Author(s), 2022. The Association for Clinical and Translational Science