TY - JOUR

T1 - The bacterial OMP amyloids modulate α-synuclein and amyloid-β aggregation

AU - Сулацкий, М.И.

AU - Белоусов, Михаил Владимирович

AU - Степаненко, О.В.

AU - Степаненко, О.В.

AU - Михайлова, Е.В.

AU - Фаюд, Хайдар

AU - Нижников, Антон Александрович

AU - Сулацкая, А.И.

PY - 2025/9/6

Y1 - 2025/9/6

N2 - Growing evidence links gut microbiota to neurodegenerative diseases, yet direct molecular interactions between bacterial and host amyloid proteins remain incompletely understood. Bacterial amyloids represent an understudied yet potentially critical component of gut-brain communication in neurodegeneration. Here, we provide the first investigation of whether amyloids formed by outer membrane proteins (OMPs) of enterobacteria can modulate neurodegeneration-associated protein aggregation. We examined the effects of pre-formed amyloid fibrils from OmpC and OmpF of Escherichia coli and Salmonella enterica on fibrillogenesis of α-synuclein and amyloid-β, whose pathological accumulation in brain is associated with Parkinson's and Alzheimer's diseases, respectively. Using a comprehensive array of physicochemical methods, we discovered that bacterial OMP amyloids altered the structural properties and clustering tendency of mammalian amyloids in a target-specific manner. In particular, for α-synuclein, OMP amyloids modified the irregular “fuzzy coat” surrounding the ordered β-core, increasing fibril clustering without affecting core structure, quantity, or cytotoxicity. In contrast, amyloid-β fibrils showed more extensive structural changes, with modifications to both the “fuzzy coat” and β-sheet core, accompanied by a decreased clustering tendency and significantly reduced toxicity for mammalian neuroblastoma and epithelial adenocarcinoma cell lines. Our findings demonstrate that amyloids formed from OMPs produced by Enterobacteriaceae species represent a previously unrecognized class of amyloid modulators capable of influencing pathological aggregation of mammalian proteins through intermolecular contacts. These results open a discussion on the dual role of bacterial amyloids in neurodegeneration, as they may be capable not only of promoting pathological amyloidogenesis but also of mitigating the toxic effects of host amyloid aggregates.

AB - Growing evidence links gut microbiota to neurodegenerative diseases, yet direct molecular interactions between bacterial and host amyloid proteins remain incompletely understood. Bacterial amyloids represent an understudied yet potentially critical component of gut-brain communication in neurodegeneration. Here, we provide the first investigation of whether amyloids formed by outer membrane proteins (OMPs) of enterobacteria can modulate neurodegeneration-associated protein aggregation. We examined the effects of pre-formed amyloid fibrils from OmpC and OmpF of Escherichia coli and Salmonella enterica on fibrillogenesis of α-synuclein and amyloid-β, whose pathological accumulation in brain is associated with Parkinson's and Alzheimer's diseases, respectively. Using a comprehensive array of physicochemical methods, we discovered that bacterial OMP amyloids altered the structural properties and clustering tendency of mammalian amyloids in a target-specific manner. In particular, for α-synuclein, OMP amyloids modified the irregular “fuzzy coat” surrounding the ordered β-core, increasing fibril clustering without affecting core structure, quantity, or cytotoxicity. In contrast, amyloid-β fibrils showed more extensive structural changes, with modifications to both the “fuzzy coat” and β-sheet core, accompanied by a decreased clustering tendency and significantly reduced toxicity for mammalian neuroblastoma and epithelial adenocarcinoma cell lines. Our findings demonstrate that amyloids formed from OMPs produced by Enterobacteriaceae species represent a previously unrecognized class of amyloid modulators capable of influencing pathological aggregation of mammalian proteins through intermolecular contacts. These results open a discussion on the dual role of bacterial amyloids in neurodegeneration, as they may be capable not only of promoting pathological amyloidogenesis but also of mitigating the toxic effects of host amyloid aggregates.

KW - Amyloid

KW - Amyloid-β

KW - Fibrillogenesis

KW - Gut-brain

KW - Microbiome

KW - Neurodegeneration

KW - Outer membrane protein

KW - Porins

KW - α-Synuclein

UR - https://www.mendeley.com/catalogue/ccd2cb6f-9e4f-3834-a5c0-9f89be75a532/

U2 - 10.1016/j.ijbiomac.2025.147485

DO - 10.1016/j.ijbiomac.2025.147485

M3 - Article

VL - 327

JO - International Journal of Biological Macromolecules

JF - International Journal of Biological Macromolecules

SN - 0141-8130

IS - 2

M1 - 147485

ER -