The role of melanin in Fonsecaea monophora pathogenicity: adhesion, fibroblast interactions, and implications for chromoblastomycosis.

Aims: Fonsecaea monophora is a pathogen of chromoblastomycosis (CBM), and melanin is one of the important virulence factors of F.monophora. Despite the crucial role fibroblasts play in inflammatory diseases, the interaction between fibroblasts and F.monophora remains poorly understood. This study investigated fibroblast responses to wild-type (WT) and polyketide synthase A gene knockout (ΔpksA) strains, aiming to elucidate the role of fungal melanin in adhesion mechanisms and the interactions between fibroblasts and pathogens.

Materials & methods: Coculture systems of fibroblasts with WT and ΔpksA strains of F.monophora were established. Adhesion and ectophosphatase activity assays evaluated fungal attachment. Cell scratch and Transwell migration assays assessed fibroblast motility. RT-qPCR and ELISA quantified collagen synthesis, myofibroblast differentiation, and apoptosis-related gene expression.

Results and conclusions: The WT strain exhibited greater adhesion and inhibited fibroblast migration, whereas the ΔpksA strain showed reduced adhesion and enhanced migration, correlating with melanin content and ectophosphatase activity. Both strains inhibited fibroblast-to-myofibroblast differentiation, collagen synthesis, and extracellular matrix deposition, contributing to tissue remodeling. These findings highlight melanin's role in F. monophora's pathogenicity and its disruption of fibroblast function, potentially delaying wound healing in CBM.