title: Strain diversity, epistasis and the evolution of drug resistance in Mycobacterium tuberculosis.
abstract: Mycobacterium tuberculosis harbours little DNA sequence diversity compared with other bacteria. However, there is mounting evidence that strain-to-strain variation in this organism has been underestimated. We review our current understanding of the genetic diversity among M. tuberculosis clinical strains and discuss the relevance of this diversity for the ongoing global epidemics of drug-resistant tuberculosis. Based on findings in other bacteria, we propose that epistatic interactions between pre-existing differences in strain genetic background, acquired drug-resistance-conferring mutations and compensatory changes could play a role in the emergence and spread of drug-resistant M. tuberculosis.
authors.affiliation: Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute (Swiss TPH), Basel, Switzerland  University of Basel, Basel, Switzerland.
authors.forename: S
authors.initials: S
authors.lastname: Borrell
authors.forename: S
authors.initials: S
authors.lastname: Gagneux
mesh_terms: D000995:Antitubercular Agents / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial; D004843:Epistasis, Genetic; D019143:Evolution, Molecular; D005838:Genotype; D006801:Humans; D017720:Molecular Epidemiology; D009169:Mycobacterium tuberculosis / Q000145:classification* / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D011110:Polymorphism, Genetic; D014376:Tuberculosis / Q000453:epidemiology / Q000382:microbiology*
chemical_list: D000995:Antitubercular Agents