Understanding anti-tuberculosis drug efficacy: rethinking bacterial populations and how we model them

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...

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Bibliographic Details
Main Authors: Dimitrios Evangelopoulos, Joana Diniz da Fonseca, Simon J. Waddell
Format: Article
Language:English
Published: Elsevier 2015-03-01
Series:International Journal of Infectious Diseases
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S1201971214017172
Description
Summary: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.
ISSN:1201-9712
1878-3511