Transcriptome analysis of multi-azole–resistant Microsporum canis isolated from a case of feline dermatophytosis

Abstract

The mechanism of multi-azole antifungal resistance in the dermatophyte Microsporum canis was investigated through a transcriptome analysis of the multi-azole–resistant strain LLP25-013. Strain LLP25-013 was cultured with and without itraconazole (ITCZ), after which total RNA was extracted from mycelial samples. Whole-RNA sequencing was performed using a DNBSEQ-G400 system. A total of 8,846 expressed genes were detected in samples of both total RNAs from both ITCZ-treated and ITCZ-free samples. Genes sequenced with more than 10,000 reads were selected from ITCZ-treated and ITCZ-free samples, and the expression levels were compared. Treatment with ITCZ upregulated the expression of 63 genes compared with no ITCZ treatment. By contrast, ITCZ treatment downregulated the expression of 253 identified genes. ITCZ addition reduced the expression of many genes in M. canis, which could be related to the broad-spectrum antifungal drug resistance of this organism. Among the upregulated genes, the ATP-binding cassette (ABC) transporter gene is involved in resistance in other dermatophytes. Co-culture of strain LLP25-013 with milbemycin and other azoles suggested that the isolate acquired azole resistance through high expression of the ABC transporter.