Dermatophytes adaptation to the human host exemplified by <i>Microsporum canis</i>

Dermatophytes are a taxonomic group of keratinophilic fungi that engender cutaneous infections across human and animal populations. The zoophilic species <i>Microsporum canis</i>, which exhibits a widespread distribution, predominantly affects domesticated felines and canines and has recently been associated with an increased risk of human adaptation. This study conducted a comparative genome analysis, validating the adaptive expression of 12 relevant genes through neutrality tests and selection pressure analyses, with a particular focus on the evolutionary mechanisms underlying the transition from zoophilic to anthropophilic <i>Microsporum</i>. The results demonstrated a high degree of consistency in the nuclear and mitochondrial genomes among the three <i>Microsporum</i> species, while significant differences were observed in protein domains. Notably, the anthropophilic species <i>M. audouinii</i> and <i>M. ferrugineum</i> exhibited more gene duplication events and expansions in domains such as MFS and Zn2Cys6 transcription factors. Among the 138 identified genes, specific protease subfamilies (e.g. S08A, M77, S53) and CAZy subfamilies (e.g. GH18, AA1, AA3) showed strong ecological correlations with either zoophilic or anthropophilic lifestyles. The key functions of these genes from these subfamilies focus on modulating sporulation, endoproteases, lipolysis, pH regulatory adaptability, chitinase, and conidial pigment biosynthesis. Microenvironmental factors such as pH, lipid concentration, and osmolarity significantly influenced the expression of these key genes. Anthropophilic strains demonstrated higher tolerance to acidic pH and enhanced keratinase activity in lipid-rich environments, with <i>M. ferrugineum</i> exhibiting the strongest osmotic tolerance. These findings highlight the inherent evolutionary dynamics and adaptive mechanisms of dermatophytes, providing valuable insights into the pathogenicity of <i>Microsporum</i>.