Integrative molecular epidemiology of Sporothrix in Latin America reveals calmodulin genotypes associated with host, clinical form and geographic distribution

Abstract Sporothrix species are the etiological agents of sporotrichosis, an emerging fungal disease of medical and veterinary importance. Molecular surveillance using publicly available databases enables the monitoring of pathogen dissemination and the identification of genetic and epidemiological patterns, particularly in endemic regions. This study aimed to perform an integrative analysis of clinical, epidemiological and phylogenetic characteristics of Sporothrix strains in Latin America based on calmodulin ( CAL ) gene sequences deposited in GenBank between 2014 and 2023. Sequences were selected according to predefined inclusion criteria, including species identification, year of deposition and availability of clinical and epidemiological metadata. Phylogenetic reconstruction was performed using MAFFT and IQ-TREE under the K2P + G4 model with 1,000 bootstrap replicates. Principal Component Analysis and Permutational Multivariate Analysis of Variance (PERMANOVA) were applied to evaluate genetic and epidemiological clustering. A total of 571 sequences were included. Sporothrix brasiliensis was the most frequent species (53.41%), predominantly associated with humans (68.52%) and felines (24.64%), followed by S. schenckii (40.28%). Phylogenetic analysis identified three clades for S. brasiliensis (b1–b3) and S. schenckii (s1–s3), whereas S. globosa formed a single, homogeneous clade (g1). Multivariate analysis resolved three clusters for each species, with S. brasiliensis showing a highly structured grouping driven strictly by the host factor (PERMANOVA Pseudo-F = 23.08, p = 0.001), while S. schenckii exhibited pronounced geographic and clinical variance partitioning (p = 0.001). The integrative interpretation of phylogenetic, multivariate, and epidemiological data indicated geographically restricted genotypes for S. brasiliensis and transnational genotypes for S. schenckii and S. globosa , as well as species-specific host and clinical associations.These findings demonstrate that CAL -based integrative analyses of publicly available data can reveal regional genetic structure and dispersion patterns of Sporothrix species, highlighting the zoonotic relevance of S. brasiliensis and supporting the need for standardized molecular surveillance strategies in Latin America.