An anti-adhesive peptide found in extracellular vesicles from Sporothrix brasiliensis and Sporothrix schenckii

<i>Sporothrix brasiliensis</i> and <i>Sporothrix schenckii</i> are major causative agents of sporotrichosis, a neglected fungal disease with growing public health relevance. These pathogens release extracellular vesicles (EVs) that contribute to host-pathogen interactions, yet their small molecule content remains unexplored. Here, we isolated EVs from both species following growth on solid medium and characterized them using nanoparticle tracking analysis, transmission electron microscopy, proteomics, and untargeted metabolomics. While EVs from each species contained distinct sets of proteins, a subset of conserved components and metabolites was identified, including the dipeptidyl peptidase IV (DPP4) inhibitor isoleucine-proline-isoleucine (IPI), previously described as a protective EV component in <i>Cryptococcus</i>. Functional assays demonstrated that both IPI and an anti-DPP4 antibody significantly impaired fungal adhesion to type I collagen. These findings reveal new layers of molecular complexity in the EVs of <i>Sporothrix</i> spp., highlight the presence of functionally conserved small molecules, and suggest a role for EV-derived peptides in modulating fungal surface interactions with host structures.