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Published on: November 6, 2019
Genomic Tandem Quadruplication is Associated with Ketoconazole Resistance in Malassezia pachydermatis
Minchul Kim1, Yong-Joon Cho2, Minji Park1
1Department of Systems Biotechnology, Chung-Ang University, Anseong 17546, Republic of Korea.
Abstract:
Malassezia pachydermatis is a commensal yeast found on the skin of dogs. However, M. pachydermatis is also considered an opportunistic pathogen and is associated with various canine skin diseases including otitis externa and atopic dermatitis, which usually require treatment using an azole antifungal drug, such as ketoconazole. In this study, we isolated a ketoconazole-resistant strain of M. pachydermatis, designated "KCTC 27587," from the external ear canal of a dog with otitis externa and analyzed its resistance mechanism. To understand the mechanism underlying ketoconazole resistance of the clinical isolate M. pachydermatis KCTC 27587, the whole genome of the yeast was sequenced using the PacBio platform and was compared with M. pachydermatis type strain CBS 1879. We found that a ~84-kb region in chromosome 4 of M. pachydermatis KCTC 27587 was tandemly quadruplicated. The quadruplicated region contains 52 protein coding genes, including the homologs of ERG4 and ERG11, whose overexpression is known to be associated with azole resistance. Our data suggest that the quadruplication of the ~84-kb region may be the cause of the ketoconazole resistance in M. pachydermatis KCTC 27587.
Insights
A new ketoconazole-resistant strain of Malassezia pachydermatis (KCTC 27587) was identified in a dog with otitis externa. Genome sequencing revealed a quadruplicated region potentially causing this antifungal resistance.
Area of Science:
- Veterinary Mycology
- Antimicrobial Resistance Research
Background:
- Malassezia pachydermatis is a common yeast on dog skin.
- It can cause opportunistic skin infections like otitis externa.
- Azole antifungals, such as ketoconazole, are standard treatments.
Purpose of the Study:
- To investigate the mechanism of ketoconazole resistance in a clinical M. pachydermatis isolate.
- To analyze the whole genome of the resistant strain KCTC 27587.
Main Methods:
- Isolation of a ketoconazole-resistant M. pachydermatis strain (KCTC 27587).
- Whole genome sequencing using the PacBio platform.
- Comparative genomic analysis with the M. pachydermatis type strain CBS 1879.
Main Results:
- A ~84-kb region on chromosome 4 was tandemly quadruplicated in the resistant strain.
- This region contains 52 protein-coding genes, including ERG4 and ERG11 homologs.
- Overexpression of ERG genes is linked to azole resistance.
Conclusions:
- The quadruplication of the ~84-kb genomic region is proposed as the cause of ketoconazole resistance in M. pachydermatis KCTC 27587.
- This finding provides insight into antifungal resistance mechanisms in veterinary pathogens.
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