Rifabutin Suppresses Inducible Clarithromycin Resistance in Mycobacterium abscessus by Blocking Induction of whiB7 and erm41.

ABSTRACT: Clarithromycin (CLR) is the corner stone in regimens for the treatment of lung disease caused by Mycobacterium abscessus (Mab). However, many strains harbor the CLR-inducible CLR resistance gene erm41, encoding a ribosome methylase. Induction of erm41 is mediated by the transcription factor whiB7. We hypothesized that an inhibitor of RNA synthesis should be able to block the whiB7-erm41 induction response to CLR exposure and thus suppress CLR resistance. Recently, we discovered that the rifampicin analog rifabutin (RFB) shows attractive potency against Mab. To determine whether RFB-CLR combinations are synergistic, a checkerboard analysis against a collection of erm41 positive and negative Mab strains was carried out. This revealed synergy of the two drugs for erm41 positive but not for er

SUBMITTER: Aziz DB 

PROVIDER: S-EPMC7168051 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature