Role of Disputed Mutations in the rpoB Gene in Interpretation of Automated Liquid MGIT Culture Results for Rifampin Susceptibility Testing of Mycobacterium tuberculosis.

ABSTRACT: Low-level rifampin resistance associated with specific rpoB mutations (referred as "disputed") in Mycobacterium tuberculosis is easily missed by some phenotypic methods. To understand the mechanism by which some mutations are systematically missed by MGIT phenotypic testing, we performed an in silico analysis of their effect on the structural interaction between the RpoB protein and rifampin. We also characterized 24 representative clinical isolates by determining MICs on 7H10 agar and testing them by an extended MGIT protocol. We analyzed 2,097 line probe assays, and 156 (7.4%) cases showed a hybridization pattern referred to here as "no wild type + no mutation." Isolates harboring "disputed" mutations (L430P, D435Y, H445C/L/N/S, and L452P) tested susceptible in MGIT,

SUBMITTER: Miotto P 

PROVIDER: S-EPMC5925711 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature