Mutations confer clarithromycin resistance in M. abscessus complex

Mycobacterium abscessus is a common nontuberculous mycobacteria pathogen that has emerged with resistance to most antimicrobial agents. One of the biggest challenges is its resistance to clarithromycin, the cornerstone drug for treating M. abscessus infections. Previous studies have shown that acquired clarithromycin resistance is predominantly due to canonical mutations in the 23S rRNA residue 2270/2271. However, clinical isolates with acquired clarithromycin resistance that lack rrl 2270/2271 mutations have been extensively reported. In this study, we selected spontaneous resistant mutants from two parental strains with different sensitivities to clarithromycin. We identified several noncanonical mutations in these mutants, in addition to the canonical ones in rrl 2270/2271.