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Plasmid-mediated macrolide resistance among rapidly growing mycobacteria in Japan
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.
Insights
The 23S rRNA methylase gene erm(55) plasmid confers inducible macrolide resistance in rapidly growing mycobacteria (RGM). This study found a low prevalence of erm(55)-carrying plasmids in Japanese RGM clinical isolates, highlighting the need for vigilance.
Area of Science:
- Microbiology
- Genetics
- Antimicrobial Resistance
Background:
- Rapidly growing mycobacteria (RGM) can acquire macrolide resistance via the 23S rRNA methylase gene, erm(55).
- The spread of erm(55)-carrying plasmids poses a clinical challenge due to inducible macrolide resistance in RGM.
- Understanding the prevalence of these plasmids is crucial for effective treatment strategies.
Purpose of the Study:
- To investigate the prevalence of erm(55)-carrying plasmids in clinically isolated RGM strains in Japan.
- To characterize the genetic features of these macrolide resistance plasmids.
Main Methods:
- Analysis of 607 RGM clinical isolates from Japan (2019-2023).
- Detection of erm(55) plasmids using PCR and minimum inhibitory concentration testing for clarithromycin.
- Whole-plasmid genome sequencing and comparative genomic analyses.
Main Results:
- The erm(55) plasmid was detected in 0.8% (5/607) of RGM isolates, conferring inducible macrolide resistance.
- Positive isolates included Mycobacterium murale, M. obuense, and M. chelonae.
- Plasmids ranged from 126,187 to 170,220 bp, with highly similar erm(55) sequences located in a horizontal gene transfer region.
Conclusions:
- The presence of macrolide-resistant RGMs carrying the erm(55) plasmid is confirmed in Japan, albeit at a low prevalence.
- These findings underscore the importance of considering plasmid-mediated resistance mechanisms in RGM infections.
- Monitoring and characterization of such resistance determinants are essential for public health.
