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Multidrug Resistance Plasmid pTZC1 Could Be Pooled among Cutibacterium Strains on the Skin Surface
Juri Koizumi1, Keisuke Nakase1, Nobukazu Hayashi2
1Department of Clinical Microbiology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, Japan.
Abstract:
Acne vulgaris is a chronic inflammatory skin disease that is exacerbated by Cutibacterium acnes. Although antimicrobials such as macrolides, clindamycin, and tetracyclines are used to treat acne caused by C. acnes, the increasing prevalence of antimicrobial-resistant C. acnes strains has become a global concern. In this study, we investigated the mechanism by which interspecies transfer of multidrug-resistant genes can lead to antimicrobial resistance. Specifically, the transfer of pTZC1 between C. acnes and C. granulosum isolated from specimens of patients with acne was investigated. Among the C. acnes and C. granulosum isolated from 10 patients with acne vulgaris, 60.0% and 70.0% of the isolates showed resistance to macrolides and clindamycin, respectively. The multidrug resistance plasmid pTZC1, which codes for macrolide-clindamycin resistance gene erm(50) and tetracycline resistance gene tet(W), was identified in both C. acnes and C. granulosum isolated from the same patient. In addition, whole-genome sequencing revealed that the pTZC1 sequences of C. acnes and C. granulosum showed 100% identity using comparative whole-genome sequencing analysis. Therefore, we hypothesize that the horizontal transfer of pTZC1 between C. acnes and C. granulosum strains may occur on the skin surface. The plasmid transfer test revealed a bidirectional transfer of pTZC1 between C. acnes and C. granulosum, and transconjugants that obtained pTZC1 exhibited multidrug resistance. In conclusion, our results revealed that the multidrug resistance plasmid pTZC1 could be transferred between C. acnes and C. granulosum. Furthermore, since pTZC1 transfer among different species may aid in the prevalence of multidrug resistant strains, antimicrobial resistance genes may have been pooled on the skin surface. IMPORTANCE The emergence of antimicrobial resistance not only in Cutibacterium acnes strain but also other skin bacteria such as Staphylococcus epidermidis is a big concern due to antimicrobial use for the treatment of acne vulgaris. Increased prevalence of macrolides-clindamycin resistant C. acnes relates to the acquisition of exogenous antimicrobial resistance genes. erm(50) is harbored by the multidrug resistance plasmid pTZC1, which has been found in C. acnes and C. granulosum strains isolated from patients with acne vulgaris. In this study, C. acnes and C. granulosum with pTZC1 were found in the same patient, and plasmid transfer between C. acnes and C. granulosum was proved by transconjugation assay. This study showed plasmid transfer between other species and the possibility of further prevalence antimicrobial resistance between Cutibacterium species.
Insights
Antimicrobial resistance in acne is rising due to gene transfer. A multidrug resistance plasmid, pTZC1, was found to transfer between Cutibacterium acnes and Cutibacterium granulosum, increasing resistance on the skin.
Area of Science:
- Microbiology
- Genetics
- Dermatology
Background:
- Acne vulgaris is a common skin condition exacerbated by Cutibacterium acnes.
- Antimicrobial resistance in C. acnes strains is a growing global health concern.
- Existing treatments for acne rely on antimicrobials like macrolides, clindamycin, and tetracyclines.
Purpose of the Study:
- To investigate the mechanism of interspecies gene transfer contributing to antimicrobial resistance.
- To examine the transfer of the multidrug resistance plasmid pTZC1 between C. acnes and C. granulosum.
Main Methods:
- Isolation and identification of C. acnes and C. granulosum from acne patients.
- Antimicrobial susceptibility testing for macrolides, clindamycin, and tetracyclines.
- Identification of the pTZC1 plasmid carrying erm(50) and tet(W) genes.
- Whole-genome sequencing for comparative analysis of pTZC1.
- Plasmid transfer assays (conjugation) to demonstrate interspecies transfer.
Main Results:
- High prevalence of macrolide (60.0%) and clindamycin (70.0%) resistance in isolated C. acnes and C. granulosum.
- The multidrug resistance plasmid pTZC1 was identified in both species from the same patient.
- pTZC1 sequences showed 100% identity between C. acnes and C. granulosum.
- Bidirectional transfer of pTZC1 between C. acnes and C. granulosum was confirmed.
- Transconjugants acquired pTZC1 and exhibited multidrug resistance.
Conclusions:
- The multidrug resistance plasmid pTZC1 can be transferred between C. acnes and C. granulosum.
- Horizontal gene transfer of pTZC1 on the skin surface contributes to the prevalence of multidrug-resistant strains.
- Antimicrobial resistance genes may pool on the skin surface, facilitating resistance spread among bacteria.
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