Susceptibility Profiles Among Sporothrix brasiliensis Genotypes in the Ongoing Zoonotic Sporotrichosis Epidemic in Brazil, Argentina and Paraguay

Sporothrix brasiliensis is the predominant etiological agent of sporotrichosis in Brazil and has been progressively expanding its geographic distribution to other countries in South America. The human patients infected with S. brasiliensis usually respond favorably to antifungal therapy. However, therapeutic failure may occur, and management may be particularly challenging in cases of severe disease. We recently reported that at least seven S. brasiliensis genotypes circulate across South America. However, their biological and clinical relevance of this genetic diversity remains poorly understood. In this study, we investigated whether distinct S. brasiliensis genotypes are associated with reduced susceptibility to the main antifungal agents used in the treatment of human and animal sporotrichosis. A total of 92 clinical, veterinary, and environmental S. brasiliensis strains from Brazil, Paraguay and Argentina, genotyping them using a four-gene MLST scheme. Mating type was assessed as well as antifungal susceptibility according to the M38-A2 CLSI guidelines. Results were interpreted according to the established epidemiological cutoff values for S. brasiliensis. The isolates are clustered into six distinct genotypes, with mating type showing a strong association with phylogenetic clades. Non-wild type strains were identified across four haplotypes (H1, H2, H3 and H4) for all antifungal drugs tested. These non-wild type strains were isolated from six distinct Brazilian states and were not associated to a specific genetic background. Nevertheless, non-wild-type strains were predominantly detected among feline isolates, most of which originated from Minas Gerais and belonged to haplotype H2. However, because only a limited number of H2 isolates were included in this study, additional isolates from this haplotype are need to confirm this association. Together, these findings suggest that decreased antifungal susceptibility in S. brasiliensis is not genotype-restricted but may be influenced by host-related or epidemiological factors, particularly in the context of feline sporotrichosis.