Comparative analysis of drug susceptibility among different Mycobacterium abscessus morphotypes

Mycobacterium abscessus (MAB), a rapidly growing non-tuberculous mycobacterium, presents severe therapeutic challenges due to its intrinsic and acquired multidrug resistance. Notably, MAB exhibits phenotypic heterogeneity, with smooth (S) and rough (R) morphotypes displaying distinct drug susceptibility phenotypes. We systematically examined the phenotypic diversity and drug susceptibility profiles of 100 clinical MAB isolates, including 79 R-type, 13 S-type, and 8 mixed (M) morphotypes. The three morphotypes (R, S, M) exhibited distinct drug resistance profiles. Both R-type and S-type strains showed broad-spectrum resistance to fluoroquinolones, tetracycline derivatives, and carbapenems. In contrast, S-type strains remained fully susceptible to clofazimine (CFZ), linezolid (LNZ), and trimethoprim-sulfamethoxazole (TMS). Notably, significant differences in resistance to capreomycin (CAP) and clofazimine (CFZ) were observed among the three morphotypes. Genotypic analysis revealed a homogeneous distribution of key resistance genes (erm(41), rrl, rrs) across morphotypes. Our findings highlight the relationship between MAB morphotypes and antibiotic resistance is complex and drug specific. It is necessary to integrate morphotype with genotypic profiling and phenotypic characterization to better understand the complex resistance landscape of MAB and to guide more effective therapeutic strategy.