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Genome Med DOI:10.1186/s13073-019-0660-8

Deciphering drug resistance in Mycobacterium tuberculosis using whole-genome sequencing: progress, promise, and challenges.

Publication TypeJournal Article
Year of Publication2019
AuthorsCohen, KA, Manson, AL, Desjardins, CA, Abeel, T, Earl, AM
JournalGenome Med
Volume11
Issue1
Pages45
Date Published2019 07 25
ISSN1756-994X
Abstract

Tuberculosis (TB) is a global infectious threat that is intensified by an increasing incidence of highly drug-resistant disease. Whole-genome sequencing (WGS) studies of Mycobacterium tuberculosis, the causative agent of TB, have greatly increased our understanding of this pathogen. Since the first M. tuberculosis genome was published in 1998, WGS has provided a more complete account of the genomic features that cause resistance in populations of M. tuberculosis, has helped to fill gaps in our knowledge of how both classical and new antitubercular drugs work, and has identified specific mutations that allow M. tuberculosis to escape the effects of these drugs. WGS studies have also revealed how resistance evolves both within an individual patient and within patient populations, including the important roles of de novo acquisition of resistance and clonal spread. These findings have informed decisions about which drug-resistance mutations should be included on extended diagnostic panels. From its origins as a basic science technique, WGS of M. tuberculosis is becoming part of the modern clinical microbiology laboratory, promising rapid and improved detection of drug resistance, and detailed and real-time epidemiology of TB outbreaks. We review the successes and highlight the challenges that remain in applying WGS to improve the control of drug-resistant TB through monitoring its evolution and spread, and to inform more rapid and effective diagnostic and therapeutic strategies.

DOI10.1186/s13073-019-0660-8
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/31345251?dopt=Abstract

Alternate JournalGenome Med
PubMed ID31345251
PubMed Central IDPMC6657377
Grant ListK08 HL139994 / HL / NHLBI NIH HHS / United States
U19AI110818 / / National Institute of Allergy and Infectious Diseases (US) / International