Transferable Multidrug-Resistance Plasmid Carrying a Novel Macrolide-Clindamycin Resistance Gene, erm(50), in
Sae Aoki1, Keisuke Nakase2, Hidemasa Nakaminami1
1Department of Microbiology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, Japan.
Abstract:
Antimicrobial-resistant Cutibacterium acnes strains have emerged and disseminated throughout the world. The 23S rRNA mutation and erm(X) gene are known as the major resistance determinants of macrolides and clindamycin in C. acnes We isolated eight high-level macrolide-clindamycin-resistant C. acnes strains with no known resistance determinants, such as 23S rRNA mutation and erm(X), from different acne patients in 2008 between 2013 and 2015. The aim of this study was to identify the novel mechanisms of resistance in C. acnes Whole-genome sequencing revealed the existence of a plasmid DNA, denoted pTZC1 (length, 31,440 bp), carrying the novel macrolide-clindamycin resistance gene erm(50) and tetracycline resistance gene tet(W). pTZC1 was detected in all C. acnes isolates (eight strains) exhibiting high-level macrolide-clindamycin resistance, with no known resistance determinants (MIC of clarithromycin, ≥256 μg/ml; clindamycin, ≥256 μg/ml). Transconjugation experiments demonstrated that the pTZC1 was horizontally transferred among C. acnes strains and conferred resistance to macrolides, clindamycin, and tetracyclines. Our data showed, for the first time, the existence of a transferable multidrug-resistant plasmid in C. acnes Increased prevalence of this plasmid will be a great threat to antimicrobial therapy for acne vulgaris.
Insights
A novel plasmid, pTZC1, carrying the erm(50) gene, confers multidrug resistance in Cutibacterium acnes. This transferable plasmid poses a significant threat to acne vulgaris antimicrobial therapy.
Area of Science:
- Microbiology
- Genetics
- Dermatology
Background:
- Antimicrobial resistance in Cutibacterium acnes is a growing global concern.
- Known resistance mechanisms, like 23S rRNA mutations and erm(X) genes, do not explain all observed resistance phenotypes.
Purpose of the Study:
- To identify novel resistance mechanisms in macrolide-clindamycin-resistant Cutibacterium acnes strains.
- To characterize the genetic basis of high-level resistance in previously unexplained C. acnes isolates.
Main Methods:
- Whole-genome sequencing of resistant C. acnes strains.
- Plasmid identification and characterization (pTZC1).
- Transconjugation experiments to assess gene transfer and conferred resistance.
Main Results:
- A novel plasmid, pTZC1, was identified, containing the erm(50) and tet(W) resistance genes.
- pTZC1 was present in all eight macrolide-clindamycin-resistant C. acnes strains lacking known resistance determinants.
- Transconjugation confirmed horizontal transfer of pTZC1, conferring resistance to macrolides, clindamycin, and tetracyclines.
Conclusions:
- A transferable multidrug-resistant plasmid (pTZC1) with a novel resistance gene (erm(50)) exists in C. acnes.
- The increasing prevalence of this plasmid threatens the efficacy of antimicrobial treatments for acne vulgaris.
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