Pseudomonas aeruginosa rhamnolipid induces fibrillation of human α-synuclein and modulates its effect on biofilm formation

Abstract

The Parkinson's disease-associated protein α-synuclein (αSN) is natively unfolded but its structure can be modulated by membranes and surfactants. The opportunistic pathogen Pseudomonas aeruginosa (PA) produces and secretes the biosurfactant rhamnolipid (RL) which modulates bacterial biofilm. Here, we show that monomeric RL enhances the ability of αSN to permeabilize membranes, while micellar RL rapidly induces protein β-sheet structure with a worm-like fibrillary appearance, which cannot seed RL-free fibrillation but transforms into linear fibrils faster than αSN fibrillating on its own. Exposure to αSN reduces the degree of biofilm formation by PA unless RL is present. Our data suggest that RL interactions with αSN may affect both αSN aggregation and cell toxicity, potentially implicating microbiomic metabolites in the origin and propagation of Parkinson's disease.