Biochemical Characterization of Isoniazid-resistant Mycobacterium tuberculosis: Can the Analysis of Clonal Strains Reveal Novel Targetable Pathways?

Molecular & Cellular Proteomics : MCP
Luisa Maria Nieto RKaren M Dobos

Abstract

Tuberculosis (TB) continues to be an important public health threat worldwide, due in part to drug resistant Mycobacterium tuberculosis (Mtb) strains. The United States recently reported a shortage of isoniazid (INH), which could drive higher INH resistance rates. Changes in the Mtb proteome before and after acquisition of INH resistance in a clean genetic background remain understudied and may elucidate alternate drug targets. Here, we focused on Mtb clonal strains to characterize the consequences of INH resistance on mycobacterial metabolism. Proteomic analysis was conducted by liquid-chromatography tandem mass spectrometry (LC-MS/MS) of cellular and secreted fractions, followed by a normalized spectral counting (NSAF) analysis (data are available via ProteomeXchange with identifier PXD009549). Two different Mtb clonal pairs representing a specific genetic lineage (one clinical and one generated in the laboratory) but sharing a katG mutation associated with INH resistance, were used in our analysis. Overall, we found 26 Mtb proteins with altered abundances after acquisition of INH resistance across both Mtb genetic lineages studied. These proteins were involved in ATP synthesis, lipid metabolism, regulatory events, and virule...Continue Reading

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Citations

Nov 20, 2020·Microbial Drug Resistance : MDR : Mechanisms, Epidemiology, and Disease·M A Abo-KadoumJianping Xie
Dec 8, 2020·Frontiers in Cellular and Infection Microbiology·Moagi ShakuBavesh D Kana
Feb 23, 2021·Frontiers in Microbiology·Anna Allué-GuardiaJordi B Torrelles
Aug 26, 2021·Computational and Structural Biotechnology Journal·Isin T SakalliogluRobert Powers
Feb 1, 2022·Omics : a Journal of Integrative Biology·Kriti AwasthiThottethodi Subrahmanya Keshava Prasad

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