Phylogenetically informative mutations in genes implicated in antibiotic resistance in Mycobacterium tuberculosis complex.

ABSTRACT:

Background

A comprehensive understanding of the pre-existing genetic variation in genes associated with antibiotic resistance in the Mycobacterium tuberculosis complex (MTBC) is needed to accurately interpret whole-genome sequencing data for genotypic drug susceptibility testing (DST).

Methods

We investigated mutations in 92 genes implicated in resistance to 21 anti-tuberculosis drugs using the genomes of 405 phylogenetically diverse MTBC strains. The role of phylogenetically informative mutations was assessed by routine phenotypic DST data for the first-line drugs isoniazid, rifampicin, ethambutol, and pyrazinamide from a separate collection of over 7000 clinical strains. Selected mutations/strains were further investigated by minimum inhibitory concentration (MIC) testing.

SUBMITTER: Merker M 

PROVIDER: S-EPMC7060619 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature