A multi-stress model for high throughput screening against non-replicating Mycobacterium tuberculosis

Methods in Molecular Biology
Ben GoldCarl Nathan

Abstract

Models of non-replication help us understand the biology of persistent Mycobacterium tuberculosis. High throughput screening (HTS) against non-replicating M. tuberculosis may lead to identification of tool compounds that affect pathways on which bacterial survival depends in such states, and to development of drugs that can overcome phenotypic tolerance to conventional antimycobacterial agents, which are mostly active against replicating M. tuberculosis. We describe a multi-stress model of non-replication that mimics some of the microenvironmental conditions that M. tuberculosis faces in the host as adapted for HTS. The model includes acidic pH, mild hypoxia, a flux of nitric oxide and other reactive nitrogen intermediates arising from nitrite at low pH, and low concentrations of a fatty acid (butyrate) as a carbon source.

Citations

Jun 14, 2017·Antimicrobial Agents and Chemotherapy·Carolina Rodrigues FelixKyle H Rohde
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Nov 16, 2019·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Michael Dal MolinPeter Sander
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