title: Understanding anti-tuberculosis drug efficacy: rethinking bacterial populations and how we model them.
abstract: Tuberculosis still remains a global health emergency, claiming 1.5 million lives in 2013. The bacterium responsible for this disease, Mycobacterium tuberculosis (M.tb), has successfully survived within hostile host environments, adapting to immune defence mechanisms, for centuries. This has resulted in a disease that is challenging to treat, requiring lengthy chemotherapy with multi-drug regimens. One explanation for this difficulty in eliminating M.tb bacilli in vivo is the disparate action of antimicrobials on heterogeneous populations of M.tb, where mycobacterial physiological state may influence drug efficacy. In order to develop improved drug combinations that effectively target diverse mycobacterial phenotypes, it is important to understand how such subpopulations of M.tb are formed during human infection. We review here the in vitro and in vivo systems used to model M.tb subpopulations that may persist during drug therapy, and offer aspirations for future research in this field.
authors: Centre for Clinical Microbiology, University College London, London, NW3 2PF, UK. Electronic address: d.evangelopoulos@ucl.ac.uk.
authors: Dimitrios
authors: D
authors: Evangelopoulos
authors: Centre for Clinical Microbiology, University College London, London, NW3 2PF, UK.
authors: Joana Diniz
authors: JD
authors: da Fonseca
authors: Brighton and Sussex Medical School, University of Sussex, Brighton, BN1 9PX, UK.
authors: Simon J
authors: SJ
authors: Waddell
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000627:therapeutic use*; D006801:Humans; D008954:Models, Biological; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D014376:Tuberculosis / Q000188:drug therapy* / Q000382:microbiology
chemical_list: D000995:Antitubercular Agents
keywords: Mycobacterium tuberculosis; drug discovery; persistence models; phenotypic drug tolerance; subpopulations