Inhibition of RhoA Prevents Cryptococcus neoformans Capsule Glucuronoxylomannan-Stimulated Brain Endothelial Barrier Disruption.

ABSTRACT: Cryptococcus neoformans (Cn) is an opportunistic fungus that causes severe central nervous system (CNS) disease in immunocompromised individuals. Brain parenchyma invasion requires fungal traversal of the blood-brain barrier. In this study, we describe that Cn alters the brain endothelium by activating small GTPase RhoA, causing reorganization of the actin cytoskeleton and tight junction modulation to regulate endothelial barrier permeability. We confirm that the main fungal capsule polysaccharide glucuronoxylomannan is responsible for these alterations. We reveal a therapeutic benefit of RhoA inhibition by CCG-1423 in vivo. RhoA inhibition prolonged survival and reduced fungal burden in a murine model of disseminated cryptococcosis, supporting the therapeutic potential of targeting RhoA i

SUBMITTER: Munzen ME 

PROVIDER: S-EPMC11481333 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature