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

Area of Science:

• Microbiology
• Neuroscience
• Biochemistry

Background:

• Gut microbiota composition is increasingly linked to neurodegenerative diseases.
• The role of bacterial amyloids in gut-brain communication and neurodegeneration is poorly understood.
• Outer membrane proteins (OMPs) of enterobacteria can form amyloid structures.

Purpose of the Study:

• To investigate if bacterial OMP amyloids modulate the aggregation of host proteins associated with neurodegeneration.
• To examine the effects of Escherichia coli and Salmonella enterica OMP amyloids on alpha-synuclein and amyloid-beta fibrillogenesis.

Main Methods:

• Formation and characterization of amyloid fibrils from OmpC and OmpF.
• Assay of bacterial OMP amyloids' effects on alpha-synuclein and amyloid-beta aggregation using physicochemical methods.
• Evaluation of cytotoxicity in mammalian cell lines.

Main Results:

• Bacterial OMP amyloids altered the structure and clustering of alpha-synuclein and amyloid-beta in a target-specific manner.
• Alpha-synuclein fibril clustering increased without affecting core structure or cytotoxicity.
• Amyloid-beta showed structural changes, decreased clustering, and significantly reduced toxicity.

Conclusions:

• Bacterial OMP amyloids represent a novel class of amyloid modulators influencing host protein aggregation.
• These interactions occur via intermolecular contacts, impacting gut-brain communication in neurodegeneration.
• Bacterial amyloids may have a dual role, potentially promoting or mitigating host amyloid toxicity.