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Antimicrobial resistance in Mycobacterium tuberculosis : mechanistic and evolutionary perspectives

Gygli, Sebastian M. and Borrell, Sonia and Trauner, Andrej and Gagneux, Sebastien. (2017) Antimicrobial resistance in Mycobacterium tuberculosis : mechanistic and evolutionary perspectives. FEMS Microbiology Reviews, 41 (3). pp. 354-373.

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Abstract

Antibiotic-resistant Mycobacterium tuberculosis strains are threatening progress in containing the global tuberculosis epidemic. Mycobacterium tuberculosis is intrinsically resistant to many antibiotics, limiting the number of compounds available for treatment. This intrinsic resistance is due to a number of mechanisms including a thick, waxy, hydrophobic cell envelope and the presence of drug degrading and modifying enzymes. Resistance to the drugs which are active against M. tuberculosis is, in the absence of horizontally transferred resistance determinants, conferred by chromosomal mutations. These chromosomal mutations may confer drug resistance via modification or overexpression of the drug target, as well as by prevention of prodrug activation. Drug resistance mutations may have pleiotropic effects leading to a reduction in the bacterium's fitness, quantifiable e.g. by a reduction in the in vitro growth rate. Secondary so-called compensatory mutations, not involved in conferring resistance, can ameliorate the fitness cost by interacting epistatically with the resistance mutation. Although the genetic diversity of M. tuberculosis is low compared to other pathogenic bacteria, the strain genetic background has been demonstrated to influence multiple aspects in the evolution of drug resistance. The rate of resistance evolution and the fitness costs of drug resistance mutations may vary as a function of the genetic background.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology > Tuberculosis Research (Gagneux)
UniBasel Contributors:Gagneux, Sebastien and Gygli, Sebastian and Borrell, Sonia
Item Type:Article, refereed
Publisher:Blackwell
ISSN:0168-6445
e-ISSN:1574-6976
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
Identification Number:
Last Modified:15 Nov 2017 10:35
Deposited On:14 Jun 2017 14:26

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