title: A multi-stress model for high throughput screening against non-replicating Mycobacterium tuberculosis.
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.
authors.affiliation: Department of Microbiology and Immunology, Weill Cornell Medical College, Belfer 1126, 413 East 69th St., New York, NY, 10065, USA, bsg2001@med.cornell.edu.
authors.forename: Ben
authors.initials: B
authors.lastname: Gold
authors.forename: Thulasi
authors.initials: T
authors.lastname: Warrier
authors.forename: Carl
authors.initials: C
authors.lastname: Nathan
mesh_terms: D000995:Antitubercular Agents / Q000494:pharmacology*; D055808:Drug Discovery / Q000379:methods; D005227:Fatty Acids / Q000378:metabolism; D057166:High-Throughput Screening Assays / Q000379:methods*; D000860:Hypoxia / Q000378:metabolism; D008826:Microbial Sensitivity Tests / Q000379:methods*; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D013312:Stress, Physiological
chemical_list: D000995:Antitubercular Agents; D005227:Fatty Acids; D009569:Nitric Oxide