Mutations in dnaA and a cryptic interaction site increase drug resistance in Mycobacterium tuberculosis.

ABSTRACT: Genomic dissection of antibiotic resistance in bacterial pathogens has largely focused on genetic changes conferring growth above a single critical concentration of drug. However, reduced susceptibility to antibiotics-even below this breakpoint-is associated with poor treatment outcomes in the clinic, including in tuberculosis. Clinical strains of Mycobacterium tuberculosis exhibit extensive quantitative variation in antibiotic susceptibility but the genetic basis behind this spectrum of drug susceptibility remains ill-defined. Through a genome wide association study, we show that non-synonymous mutations in dnaA, which encodes an essential and highly conserved regulator of DNA replication, are associated with drug resistance in clinical M. tuberculosis strains. We demonstrate that these d

SUBMITTER: Hicks ND 

PROVIDER: S-EPMC7738170 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature