Genome variation of Sporothrix schenckii and Sporothrix brasiliensis

Abstract

Sporotrichosis, a subcutaneous mycosis caused by dimorphic fungi of the Sporothrix genus, has become a major zoonotic epidemic in South America, primarily driven by Sporothrix brasiliensis. To elucidate the genomic basis of its emergence and antifungal adaptation, we analyzed whole-genome sequences from 95 Sporothrix isolates, integrating single-nucleotide polymorphism (SNP), copy number variation (CNV), and genome-wide association (GWAS) analyses. Comparative genomics revealed 610,242 SNPs within S. brasiliensis and 1,474,627 within S. schenckii, confirming a marked disparity in intraspecific diversity. Phylogenomic tree inference resolved six well-supported S. brasiliensis clades with limited internal divergence, reflecting recent population expansion, while S. schenckii displayed deep phylogeographic structure separating North and South American lineages. CNV profiling identified 158 affected genes in S. brasiliensis (60 gains, 98 losses) and 88 in S. schenckii (54 gains, 34 losses), concentrated near sub-telomeric regions. In S. brasiliensis, gains were enriched for kinases and intracellular trafficking functions, whereas losses involved genes related to translation and primary metabolism, suggesting regulatory reinforcement coupled with metabolic streamlining. A GWAS of itraconazole resistance identified 81 SNPs distributed across multiple scaffolds, with many located within genes related with transport, signaling, and redox balance, supporting a polygenic basis for azole response. The implication of these alleles with itraconazole resistance warrants experimental followup. Together, these results highlight distinct evolutionary strategies of closely related Sporothrix species and pinpoint genomic changes potentially associated with the emergence and drug tolerance of S. brasiliensis. Author summary: Sporotrichosis is a fungal disease that affects humans and animals and has become an important public health problem in South America. The disease is often transmitted from infected cats to humans and is mainly caused by Sporothrix brasiliensis, although related species such as Sporothrix schenckii also cause human infections. In this study, we analyzed whole-genome data from S. brasiliensis and S. schenckii isolates to better understand how these fungi are evolving, spreading, and responding to antifungal treatment. We found that S. brasiliensis has a more clonal population structure, consistent with recent epidemic expansion, whereas S. schenckii shows deeper geographic separation between North and South American lineages. We also identified genome regions affected by copy number variation, suggesting that structural changes may contribute to adaptation in these fungi. Finally, we detected genetic variants associated with itraconazole response. The contribution of these alleles will need to be followed up with functional genetics assays. These findings provide a genomic framework for surveillance of sporotrichosis and for future studies on fungal emergence and antifungal resistance.

Original publication: PLOS Neglected Tropical Diseases (2026-09-21). Source. Source DOI: 10.1371/journal.pntd.0014203.