Advanced cellular systems to study tuberculosis treatment.

Mycobacterium tuberculosis (Mtb) kills more humans than any other infection and drug resistant strains are progressively emerging. Whilst the successful development of new agents for multi-drug resistant Mtb represents a major step forward, this progress must be balanced against recent disappointments in treatment-shortening trials. Consequently, there is a pressing need to strengthen the pipeline of drugs to treat tuberculosis (TB) and develop innovative therapeutic regimes. Approaches that bridge diverse disciplines are likely to be required to provide systems that address the limitations of current experimental models. Mtb is an obligate human pathogen that has undergone extensive co-evolution, resulting in a complex interplay between the host and pathogen. This chronic interaction involves multiple micro-environments, which may underlie some of the challenges in developing new drugs. The authors propose that advanced cell culture models of TB are likely to be an important addition to the experimental armamentarium in developing new approaches to TB, and here we review recent progress in this area and discuss the principal challenges.