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 - This article is protected by copyright. All rights reserved.

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.

KW - Pseudomonas aeruginosa

KW - amyloid

KW - biofilm

KW - biosurfactant

KW - rhamnolipid

KW - α-synuclein

UR - http://www.scopus.com/inward/record.url?scp=85044932357&partnerID=8YFLogxK

U2 - 10.1002/1873-3468.13038

DO - 10.1002/1873-3468.13038

M3 - Journal article

C2 - 29572816

SN - 0014-5793

VL - 592

SP - 1484

EP - 1496

JO - FEBS Letters

JF - FEBS Letters

IS - 9

ER -