Genomic Basis of Zoonotic Transmission and Antifungal Resistance in Microsporum canis

Microsporum canis is a globally prevalent zoonotic dermatophyte and the major causative agent of dermatophytosis in both pets and humans. The widespread clinical use of antifungal drugs has led to the frequent emergence of decreased susceptibility, while its molecular features and the genomic basis of cross-host transmission remain incompletely elucidated. In this study, 38 clinical M. canis isolates were collected from dogs and cats in Beijing (2025). We determined the minimum inhibitory concentrations (MICs) of six common antifungal agents via microbroth dilution, and performed whole-genome sequencing and comparative genomic analysis. All isolates showed high clonal homogeneity, with ANI >99.9% to the reference. A local human-derived strain was nested within the pet-derived clade, supporting zoonotic cross-host transmission. Terbinafine exhibited the highest activity, while itraconazole, voriconazole, posaconazole, griseofulvin, and ciclopirox olamine showed higher MICs; 11 isolates showed a multidrug high-MIC phenotype. Notably, copy number variation in the ABC transporter gene CDR1 was positively correlated with MICs of multiple antifungal agents (p<0.05). This study provides a genomic basis for optimized antifungal therapy, resistance surveillance and transmission control of zoonotic M. canis.