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

The Parkinson's disease-associated protein alpha-synuclein (alpha SN) 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 alpha SN to permeabilize membranes, while micellar RL rapidly induces protein beta-sheet structure with a worm-like fibrillary appearance, which cannot seed RL-free fibrillation but transforms into linear fibrils faster than alpha SN fibrillating on its own. Exposure to alpha SN reduces the degree of biofilm formation by PA unless RL is present. Our data suggest that RL interactions with alpha SN may affect both alpha SN aggregation and cell toxicity, potentially implicating microbiomic metabolites in the origin and propagation of Parkinson's disease.