phospholipase B1 is critical for cryptococcoma formation in the mouse brain.

Abstract

BACKGROUND: is an encapsulated, neurotrophic fungus that can cause life-threatening meningoencephalitis in immunocompromised individuals. Phospholipase B1 (PLB1) promotesadhesion and colonization, however its role in fungal biofilm formation is not entirely clear. METHODS: We investigated how PLB1 is involved ininfection using a stereotaxic intracerebral infection mouse model, microscopy, whole-genome sequencing, and biophysical methods. RESULTS: Our results showed that thedisrupted strain exhibited reduced survival and capsular polysaccharide (CPS) dissemination throughout brain tissue and elicited a stronger microglial response. Moreover,adhesion to SH-SY5Y human neuroblastoma cells was weakened in thedisrupted strain, andbiofilm formation showed reduced metabolic activity and thickness. Both thedisrupted and -reconstituted strains showed structural alterations; nevertheless, CPS production was increased in the-disrupted cells. We show that PLB1 is essential for maintaining capsular elasticity, regulating CPS secretion, and biofilm formation, which are critical for fungal colonization and cryptococcoma formation. CONCLUSION: These results emphasize the need for further investigation into the mechanisms underlying the pathogenicity of. In addition, our findings provide further evidence to validate PLB1 as an important antifungal target.