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Authors: P. Thomas, S. S. Nair, M. Y. Abdel-Glil, S. K. Prajapati, S. Anbazhagan, S. Saini, A. V, B. Kumar, V. K. Chaturvedi, S. M. Rudramurthy, G. Saikumar, P. Dandapat and Abhishek
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BACKGROUND: Trichophyton indotineae (earlier Trichophyton mentagrophytes ITS genotype VIII) is a newly defined dermatophyte species frequently reported from India. The strains representing T. indotineae cause dermatophytosis in humans, and some strains exhibit resistance to terbinafine. OBJECTIVE: This study aims to characterize the animal strains of T. indotineae at the genomic level and compare them with human strains and other Trichophyton species. METHODS: In this study, we report the generation of de novo WGS data for two strains of T. indotineae isolated from canines of northern India. The genome sequence was subjected to functional and structural annotation, followed by comparative genomics and phylogeny. RESULTS: Genome assembly and annotation revealed a 22 Mb genome in both strains, comprising approximately 6800 protein-coding genes, and a 24 Kb contig representing the mitochondrion. Functional annotations revealed the presence of around 200 CAZymes and secretomes. The identified proteins include various proteolytic enzymes, such as keratinases, lyases, fungalysins, subtilisins, and chitinases. Orthologous cluster comparison among T. indotineae and T. rubrum identified a LysM effector virulence factor associated with the sequestration of chitin oligosaccharides unique to T. indotineae. Taxonomic inferences involving 69 species representing the Genus Trichophyton revealed similar clustering in genome ANI, mash distance, and core-genome phylogeny. Within all approaches, a total of 16 Indian strains represented T. indotineae. The SNP difference between any two T. indiotinae strains ranged from 8 to 257, indicating limited strain variation within the species. The core-genome phylogeny revealed two major clusters, with no cluster indicating a specific host association. Correlating their phenotypic susceptibility to the anti-fungal drug terbinafine (TRB), the coding sequences (CDS) maintained no amino acid substitutions at key positions 393 and 397. The comparative analysis of the squalene epoxidase gene across the 16 strains revealed a high frequency of SNPs at the 397th position in the squalene epoxidase genes in terbinafine-resistant strains. CONCLUSION: To conclude, the study indicates similar genome composition in strains of T. indiotineae from canine and human origin, irrespective of the TRB resistance phenotype. The pathogen and genotypes circulating among humans and animals need to be continuously monitored to determine the exact role of animals in the transmission and endemicity of T. indotineae in India.
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