Rapidly Correcting Frameshift Mutations in the Mycobacterium tuberculosis <i>orn</i> Gene Produce Reversible Ethambutol Resistance and Small-Colony-Variant Morphology.

ABSTRACT: We have identified a previously unknown mechanism of reversible high-level ethambutol (EMB) resistance in Mycobacterium tuberculosis that is caused by a reversible frameshift mutation in the M. tuberculosisorn gene. A frameshift mutation in orn produces the small-colony-variant (SCV) phenotype, but this mutation does not change the MICs of any drug for wild-type M. tuberculosis However, the same orn mutation in a low-level EMB-resistant double embB-aftA mutant (MIC = 8 μg/ml) produces an SCV with an EMB MIC of 32 μg/ml. Reversible resistance is indistinguishable from a drug-persistent phenotype, because further culture of these orn-embB-aftA SCV mutants results in rapid reversion of the orn frameshifts, reestablishing the corre

SUBMITTER: Safi H 

PROVIDER: S-EPMC7449195 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature