MAB_2355c Confers Macrolide Resistance in Mycobacterium abscessus by Ribosome Protection

Abstract

Macrolide resistance is always a concern when treating Mycobacterium abscessus infections. MAB_2355c was identified previously as a possible new factor that confers the intrinsic resistance of 194 clinical M. abscessus isolates to clarithromycin. ABSTRACT Macrolide resistance is always a concern when treating Mycobacterium abscessus infections. MAB_2355c was identified previously as a possible new factor that confers the intrinsic resistance of 194 clinical M. abscessus isolates to clarithromycin. Herein, the potential mechanism by which MAB_2355c exerts macrolide resistance was explored by bioinformatics analysis, MAB_2355c cloning and protein purification, ATP hydrolysis assay, gene knockout and complementation, antibiotic sensitivity, and transcription-translation assays. MAB_2355c is a putative ATP-binding cassette F (ABC-F) family protein. Purified MAB_2355c protein exhibits ATP hydrolysis activity, which can be inhibited by ribosome-targeting antibiotics. MAB_2355c mRNA expression is upregulated more significantly after exposure to macrolides than after exposure to other ribosome-targeting antibiotics. MAB_2355c deleted strains showed increased sensitivity to macrolides, which was reduced by MAB_2355c complementation. Finally, MAB_2355c rescued the transcription and translation activities affected by macrolides in vitro. These findings suggest that MAB_2355c confers the resistance of M. abscessus to macrolides by ribosome protection, thus complementing other known resistance mechanisms.