Xin Tengteng, Wu Yushi, Zhang Junmin
Department of Dermatology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China.
Future Microbiol. 2025 Apr;20(6):449-456. doi: 10.1080/17460913.2025.2480973. Epub 2025 Mar 20.
is a pathogen of chromoblastomycosis (CBM), and melanin is one of the important virulence factors of . Despite the crucial role fibroblasts play in inflammatory diseases, the interaction between fibroblasts and remains poorly understood. This study investigated fibroblast responses to wild-type (WT) and polyketide synthase A gene knockout () 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 strains of 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.
The WT strain exhibited greater adhesion and inhibited fibroblast migration, whereas the 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 's pathogenicity and its disruption of fibroblast function, potentially delaying wound healing in CBM.
是着色芽生菌病（CBM）的病原体，黑色素是其重要的毒力因子之一。尽管成纤维细胞在炎症性疾病中发挥着关键作用，但成纤维细胞与之间的相互作用仍知之甚少。本研究调查了成纤维细胞对野生型（WT）和聚酮合酶A基因敲除（）菌株的反应，旨在阐明真菌黑色素在黏附机制以及成纤维细胞与病原体之间相互作用中的作用。
建立了成纤维细胞与WT和菌株的共培养系统。黏附及外磷酸酶活性测定评估真菌附着情况。细胞划痕和Transwell迁移测定评估成纤维细胞的运动性。RT-qPCR和ELISA定量胶原蛋白合成、肌成纤维细胞分化及凋亡相关基因表达。
WT菌株表现出更强的黏附性并抑制成纤维细胞迁移，而菌株黏附性降低且迁移增强，这与黑色素含量和外磷酸酶活性相关。两种菌株均抑制成纤维细胞向肌成纤维细胞的分化、胶原蛋白合成及细胞外基质沉积，促进组织重塑。这些发现突出了黑色素在致病过程中的作用及其对成纤维细胞功能的破坏，可能会延迟CBM中的伤口愈合。
