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.

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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