title: The heterogeneous evolution of multidrug-resistant Mycobacterium tuberculosis.
abstract: Recent surveillance data of multidrug-resistant tuberculosis (MDR-TB) reported the highest rates of resistance ever documented. As further amplification of resistance in MDR strains of Mycobacterium tuberculosis occurs, extensively drug-resistant (XDR) and totally drug-resistant (TDR) TB are beginning to emerge. Although for the most part, the epidemiological factors involved in the spread of MDR-TB are understood, insights into the bacterial drivers of MDR-TB have been gained only recently, largely owing to novel technologies and research in other organisms. Herein, we review recent findings on how bacterial factors, such as persistence, hypermutation, the complex interrelation between drug resistance and fitness, compensatory evolution, and epistasis affect the evolution of multidrug resistance in M. tuberculosis. Improved knowledge of these factors will help better predict the future trajectory of MDR-TB, and contribute to the development of new tools and strategies to combat this growing public health threat.
authors.affiliation: Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland; University of Basel, Basel, Switzerland.
authors.forename: Borna
authors.initials: B
authors.lastname: Müller
authors.forename: Sonia
authors.initials: S
authors.lastname: Borrell
authors.forename: Graham
authors.initials: G
authors.lastname: Rose
authors.forename: Sebastien
authors.initials: S
authors.lastname: Gagneux
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000494:pharmacology / Q000627:therapeutic use; D005075:Biological Evolution; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics*; D004843:Epistasis, Genetic; D056084:Genetic Fitness; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics*; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy / Q000382:microbiology*
chemical_list: D000995:Antitubercular Agents