Emerging Targets in Anti-Tubercular Drug Design

Tuberculosis (TB) is currently the second most lethal infection following HIV. In 2014 alone, there were 9.6 million new cases of TB and 1.5 million TB-related deaths reported worldwide. It is also estimated that about one third of the entire population carries latent Mycobacterium tuberculosis (Mtb), the etiological cause of TB. These individuals are asymptomatic, but can develop a full TB infection if left untreated. The current first-line TB treatment consists of a cocktail of isoniazid, rifampicin, pyrazinamide, and ethambutol. A fraction of Mtb strains develop resistance to isoniazid and rifampicin and are usually treated with second-line anti-tubercular agents, such as aminoglycosides, fluoroquinolones, or the antimicrobial peptide capreomycin. Some strains acquire further resistance to second-line treatments, causing a significantly higher mortality rate. The increase of drug-resistant Mtb strains has triggered action in the scientific field, which has led to a renaissance in anti-tubercular drug discovery with multiple emerging drug targets. Herein, we summarize the latest enzymes, pathways, and mechanisms presented in the literature (covering 2000-2016) related to the emergence of promising targets in anti-tubercular drug design.