Plasmid-mediated macrolide resistance among rapidly growing mycobacteria in Japan

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ABSTRACT Objectives The spread of a transmissible plasmid carrying the 23S rRNA methylase gene erm (55), which confers inducible macrolide resistance in rapidly growing mycobacteria (RGM), has raised significant clinical concerns. The aim of this study was to investigate the prevalence of erm (55)-carrying plasmids in clinically isolated RGM strains in Japan. Methods In total, 607 RGM clinical isolates, representing 32 species or complexes, collected between 2019 and 2023 in Japan were examined. To detect the presence of erm (55)-carrying plasmids, we conducted PCR screening, minimum inhibitory concentration testing for clarithromycin, and whole-plasmid genome sequencing. Comparative genomic analyses were performed to characterise the plasmids. Results Among the 607 RGM isolates, 0.8% (5/607) possessed the plasmid with the erm (55) gene and exhibited inducible macrolide resistance, with ratios of 100% (1/1) in Mycobacterium murale , 50% (3/6) in M. obuense , and 0.8% (1/125) in M. chelonae . The erm (55)-carrying plasmids ranged from 126,187 to 170,220 bp in size. Pairwise BLASTn comparisons of the erm (55)-carrying plasmids showed weighted percent identity values ranging from 99.5% to 99.9%, with query and subject coverage values ranging from 74.2% to 100%. All erm (55) sequences (813 bp) were identical and located within a horizontal gene transfer region. Conclusions This study confirmed the presence of macrolide-resistant RGMs related to the erm (55)-carrying plasmid in Japan, although the overall prevalence remains low. These findings emphasise the need to consider plasmid-mediated resistance when treating infections caused by the RGM species.

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