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.
|Title of host publication||Allosterism in Drug Discovery|
|Editors||David Thurston, Troy Lister, Steven M. Firestine|
|Number of pages||63|
|State||Published - 2017|
|Name||RSC Drug Discovery Series|
Bibliographical noteFunding Information:
The author is grateful to Gwenola Auda-Boucher and Yvonnick Cheraud for their collaboration during this research, Martine Molina for typing the manuscript, Felix Crossin for contributing photographic materials, Thierry Rouaud and Maryvonne Zampieri for their technical assistance, and Dr. James Gray for reading the manuscript. This work was supported by the University of Nantes, the Centre National de la Recherche Scientifique, and the Association Franeaise contre les Myopathies.
© The Royal Society of Chemistry 2017.
ASJC Scopus subject areas
- Drug Discovery