Identification of novel mutations associated with clofazimine resistance in Mycobacterium tuberculosis.

ABSTRACT:

Objectives

Although clofazimine has been traditionally used to treat leprosy, there is recent interest in using clofazimine for the treatment of MDR-TB and drug-susceptible TB. However, the mechanisms of resistance to clofazimine are poorly understood. Here, we investigated the molecular basis of clofazimine resistance using resistant mutants isolated in vitro.

Methods

We isolated 96 mutants of Mycobacterium tuberculosis resistant to clofazimine and performed WGS and Sanger sequencing to identify possible mutations associated with clofazimine resistance.

Results

We found that 97% (93/96) of clofazimine-resistant mutants had a mutation in rv0678 encoding a transcription repressor for efflux pump MmpL5. Two mutational hot spots at nucleotide positions 193 and 466 in rv0

SUBMITTER: Zhang S 

PROVIDER: S-EPMC4539095 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature