Genomic epidemiology and antifungal resistance of emerging Trichophyton indotineae in China

The emergence and spread of antifungal-resistant Trichophyton indotineae pose an increasing public health concern worldwide. Multidrug-resistant T. indotineae infections have been reported in China in the past few years. To understand the genetic relationship and the origin of these Chinese isolates, as well as their relationship to the global collections, we sequenced the whole genomes of 31 isolates using the Illumina platforms. Genomic epidemiology was performed on a dataset of 181 T. indotineae isolates from China and 8 other countries, representing the largest genome-wide analysis. Single nucleotide polymorphism analysis revealed that T. indotineae can be divided into four distinct phylogenetic groups (I, II, III, IV), with regional clonal transmission clusters identified in eastern China; T. indotineae was introduced into China more than once given the genetic variability. The isolates from South Asia may be the source of Chinese isolates based on epidemiological information. There were differences in the prevalence and resistance profiles among four phylogenetic groups, with Group III being predominant and exhibiting a higher terbinafine resistance rate of 88.24% and azole resistance. Also, we characterized the role of gene mutation, copy number variation, and gene expression in antifungal drug resistance. Terbinafine resistance could be mainly associated with Phe397Leu substitution in SQLE, and azole resistance might be related to increased copy number of CYP51B, as well as elevated MDR2 and MDR3 expression. Given the clinical challenges posed by T. indotineae, this emerging dermatophyte should be recognized as a global threat, necessitating urgent collaborative surveillance and management strategies.