# Cryptococcus neoformans phospholipase B1 is critical for cryptococcoma formation in the mouse brain

## TL;DR

This study shows that the enzyme PLB1 in Cryptococcus neoformans is crucial for the fungus to form brain infections and survive in mice.

## Contribution

The study reveals that PLB1 is essential for capsular elasticity, CPS regulation, and biofilm formation in Cn.

## Key findings

- PLB1 disruption reduces fungal survival and CPS dissemination in the brain.
- PLB1 is necessary for Cn adhesion to human neuroblastoma cells and biofilm formation.
- PLB1 influences capsular elasticity and CPS production, which are vital for cryptococcoma formation.

## Abstract

Cryptococcus neoformans (Cn) is an encapsulated, neurotrophic fungus that can cause life-threatening meningoencephalitis in immunocompromised individuals. Phospholipase B1 (PLB1) promotes Cn adhesion and colonization, however its role in fungal biofilm formation is not entirely clear.

We investigated how PLB1 is involved in Cn infection using a stereotaxic intracerebral infection mouse model, microscopy, whole-genome sequencing, and biophysical methods.

Our results showed that the PLB1-disrupted strain exhibited reduced survival and capsular polysaccharide (CPS) dissemination throughout brain tissue and elicited a stronger microglial response in vivo. Moreover, Cn adhesion to SH-SY5Y human neuroblastoma cells was weakened in the PLB1-disrupted strain, and in vitro biofilm formation showed reduced metabolic activity and thickness. Both the PLB1-disrupted and -reconstituted strains showed structural alterations; nevertheless, CPS production was increased in the PLB1-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.

These results emphasize the need for further investigation into the mechanisms underlying the pathogenicity of Cn. In addition, our findings provide further evidence to validate PLB1 as an important antifungal target.