Epistasis between antibiotic resistance mutations drives the evolution of extensively drug-resistant tuberculosis.

ABSTRACT:

Background and objectives

Multidrug resistant (MDR) bacteria are a growing threat to global health. Studies focusing on single antibiotics have shown that drug resistance is often associated with a fitness cost in the absence of drug. However, little is known about the fitness cost associated with resistance to multiple antibiotics.

Methodology

We used Mycobacterium smegmatis as a model for human tuberculosis (TB) and an in vitro competitive fitness assay to explore the combined fitness effects and interaction between mutations conferring resistance to rifampicin (RIF) and ofloxacin (OFX); two of the most important first- and second-line anti-TB drugs, respectively.

Results

We found that 4 out of 17 M. smegmatis mutants (24%) resistant to RIF and OFX showed a statisti

SUBMITTER: Borrell S 

PROVIDER: S-EPMC3868377 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature