Genomic analysis identifies targets of convergent positive selection in drug-resistant Mycobacterium tuberculosis
UMass Chan Affiliations
Commonwealth Medicine, Massachusetts Supranational TB Reference LaboratoryDocument Type
Journal ArticlePublication Date
2013-10-01Keywords
DNA RepairDrug Resistance, Microbial
Mutation
Mycobacterium tuberculosis
*Selection, Genetic
Bacteriology
Genetics and Genomics
Genomics
Immunology and Infectious Disease
Microbiology
Metadata
Show full item recordAbstract
M. tuberculosis is evolving antibiotic resistance, threatening attempts at tuberculosis epidemic control. Mechanisms of resistance, including genetic changes favored by selection in resistant isolates, are incompletely understood. Using 116 newly sequenced and 7 previously sequenced M. tuberculosis whole genomes, we identified genome-wide signatures of positive selection specific to the 47 drug-resistant strains. By searching for convergent evolution--the independent fixation of mutations in the same nucleotide position or gene--we recovered 100% of a set of known resistance markers. We also found evidence of positive selection in an additional 39 genomic regions in resistant isolates. These regions encode components in cell wall biosynthesis, transcriptional regulation and DNA repair pathways. Mutations in these regions could directly confer resistance or compensate for fitness costs associated with resistance. Functional genetic analysis of mutations in one gene, ponA1, demonstrated an in vitro growth advantage in the presence of the drug rifampicin.Source
Nat Genet. 2013 Oct;45(10):1183-9. doi: 10.1038/ng.2747. Epub 2013 Sep 1. Link to article on publisher's siteDOI
10.1038/ng.2747Permanent Link to this Item
http://hdl.handle.net/20.500.14038/30476PubMed ID
23995135Notes
Full author list omitted for brevity. For the full list of authors, see article.
Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1038/ng.2747