Genetic diversity and molecular evolution of 3-carboxymuconate cyclase (Gp60–70), the major antigen in pathogenic <i>Sporothrix</i> species

Sporotrichosis, a neglected tropical disease caused by <i>Sporothrix</i> species, is a growing concern, particularly due to the emergence of highly virulent, cat-transmitted <i>S. brasiliensis</i>. Rapid diagnosis and surveillance are crucial for controlling sporotrichosis. This study investigated the 3-carboxymuconate cyclase (<i>CMC</i>) gene, which encodes the major <i>Sporothrix</i> antigen (Gp60-70), as a molecular marker to understand the genetic diversity and evolution of these fungi. Analysis of 104 isolates (<i>S. brasiliensis</i>, S. <i>schenckii</i>, <i>S. globosa</i>, and <i>S. luriei</i>) revealed 79 unique haplotypes, demonstrating superior discriminatory power over traditional molecular markers. High-<i>CMC</i> polymorphisms, especially in <i>S. brasiliensis</i> and <i>S. schenckii</i>, suggest recent population expansion or positive selection, potentially driven by environmental pressures such as polyaromatic hydrocarbon pollutants. The conserved chromosomal location of <i>CMC</i> in pathogenic <i>Sporothrix</i> and its absence in less virulent species suggest a role in virulence. Identifying conserved residues within predicted B-cell epitopes provides targets for diagnostics and therapeutics. Additionally, we identified <i>N</i>-linked glycosylation sequons (e.g. NGS at 62, NNT at 225, and NGT at 373/374) conserved in pathogenic <i>Sporothrix</i> but absent in environmental <i>Sordariomycetes</i>, possibly contributing to pathogenicity and niche adaptation. This study establishes <i>CMC</i> as a valuable marker for understanding <i>Sporothrix</i> evolution and virulence, aiding in sporotrichosis management.