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

TY - JOUR

T1 - Pseudomonas aeruginosa rhamnolipid induces fibrillation of human α‐synuclein and modulates its effect on biofilm formation

AU - Andersen, Kell K

AU - Vad, Brian S

AU - Kjaer, Lars

AU - Tolker-Nielsen, Tim

AU - Christiansen, Gunna

AU - Otzen, Daniel E

N1 - © 2018 Federation of European Biochemical Societies.

PY - 2018/5

Y1 - 2018/5

N2 - 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.

AB - 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.

U2 - 10.1002/1873-3468.13038

DO - 10.1002/1873-3468.13038

M3 - Letter

C2 - 29572816

SN - 0014-5793

VL - 592

SP - 1484

EP - 1496

JO - F E B S Letters

JF - F E B S Letters

IS - 9

ER -