In vitro drug discovery models for Mycobacterium tuberculosis relevant for host infection

Abstract

Introduction: Tuberculosis is the leading cause of death from infectious disease. Current drug therapy requires a combination of antibiotics taken over >6 months. An urgent need for new agents that can shorten therapy is required. In order to develop new drugs, simple in vitro assays are required that can identify efficacious compounds rapidly and predict in vivo activity in the human.Areas covered: This review focusses on the most relevant in vitro assays that can be utilized in a drug discovery program and which mimic different aspects of infection or disease. The focus is largely on assays used to test >1000s of compounds reliably and robustly. However, some assays used for 10s to 100s of compounds are included where the utility outweighs the low capacity. Literature searches for high throughput screening, models and in vitro assays were undertaken.Expert opinion: Drug discovery and development in tuberculosis is extremely challenging due to the requirement for predicting drug efficacy in a disease with complex pathology in which bacteria exist in heterogeneous states in inaccesible locations. A combination of assays can be used to determine profiles against replicating, non-replicating, intracellular and tolerant bacteria.

Keywords: Anti-bacterial; Anti-tubercular; High throughput screening; Infection models; Tuberculosis.