Mechanisms of drug resistance in Mycobacterium tuberculosis: update 2015.

Drug-resistant tuberculosis (DR-TB), including multi- and extensively drug-resistant TB, is posing a significant challenge to effective treatment and TB control worldwide. New progress has been made in our understanding of the mechanisms of resistance to anti-tuberculosis drugs. This review provides an update on the major advances in drug resistance mechanisms since the previous publication in 2009, as well as added information on mechanisms of resistance to new drugs and repurposed agents. The recent application of whole genome sequencing technologies has provided new insight into the mechanisms and complexity of drug resistance. However, further research is needed to address the significance of newly discovered gene mutations in causing drug resistance. Improved knowledge of drug resistance mechanisms will help understand the mechanisms of action of the drugs, devise better molecular diagnostic tests for more effective DR-TB management (and for personalised treatment), and facilitate the development of new drugs to improve the treatment of this disease.