Genomic Tandem Quadruplication is Associated with Ketoconazole Resistance in.

Abstract

is a commensal yeast found on the skin of dogs. However,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, 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 isolateKCTC 27587, the whole genome of the yeast was sequenced using the PacBio platform and was compared withtype strain CBS 1879. We found that a ~84-kb region in chromosome 4 ofKCTC 27587 was tandemly quadruplicated. The quadruplicated region contains 52 protein coding genes, including the homologs ofand, 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 inKCTC 27587.