Plasmid-mediated macrolide resistance among rapidly growing mycobacteria in Japan

Plasmids carrying the 23S rRNA methylase gene erm(55), which confers inducible macrolide resistance in rapidly growing mycobacteria (RGM), have been reported in the United States. The aim of this study was to investigate the prevalence and genomic characteristics of erm(55)-carrying plasmids in clinically isolated RGM strains in Japan.

In total, 607 RGM clinical isolates, representing 32 species or complexes, collected between 2019 and 2023 in Japan were examined. Detection of erm(55)-carrying plasmids was conducted using PCR screening, minimum inhibitory concentration testing for clarithromycin and whole-plasmid genome sequencing. Comparative genomic analyses were performed to characterize the plasmids.

Five strains belonging to Mycobacterium murale, M. obuense and M. chelonae harboured plasmids carrying the erm(55) gene and exhibited inducible macrolide resistance, corresponding to a prevalence of 0.8%. The erm(55)-carrying plasmids ranged from 126 187 to 170 220 bp in size. The plasmids showed high overall sequence similarity, and all erm(55) sequences were identical to that of the previously reported plasmid pMchErm55 from the United States. Genes predicted to be involved in conjugation-like transfer mechanisms were conserved across all plasmids, whereas regions containing insertion sequence elements and mercury resistance genes exhibited gene content variability.

erm(55)-carrying plasmids were identified among clinical RGM isolates in Japan, although their overall prevalence was low. To date, erm(55)-carrying plasmids have been identified in at least seven Mycobacterium species. Further studies are required to assess their presence among RGM and to clarify their functional characteristics.