Bacterial OMP amyloids act as the modulators of pathological aggregation

Introduction: Bacterial amyloids are an under-researched yet potentially key factor in gut-brain communication related to neurodegeneration. In this study, we explore for the first time whether amyloid structures formed by outer membrane proteins (OMPs) of enterobacteria can influence the aggregation of proteins linked to neurodegeneration.

Objectives: We analyzed for the first time how pre-formed amyloid fibrils OmpC and OmpF from Escherichia coli and Salmonella enterica affect the fibril formation of α-synuclein and amyloid-β — proteins whose abnormal buildup in the brain is tied to Parkinson’s and Alzheimer’s diseases, respectively.

Methods: SDS-PAGE, transmission electron microscopy, amyloid-specific dye binding, and circular dichroism methods were used.

Results: For α-synuclein, OMP amyloids altered the disordered "fuzzy coat" surrounding the structured β-core, enhancing fibril clustering without changing the core’s architecture, overall quantity, or cell toxicity. In contrast, amyloid-β fibrils underwent more significant structural changes, affecting both the fuzzy coat and the β-sheet core, while reducing aggregation propensity and markedly decreasing toxicity in neuroblastoma and epithelial adenocarcinoma cells (Sulatsky & Belousov et al., Int. J. Biol. Macromol., 2025).

Conclusion: Our study reveals that OMP-derived amyloids from Enterobacteriaceae represent a previously unknown class of amyloid modulators that can shape the pathological aggregation of mammalian proteins through molecular interactions. These findings raise new questions about the dual role of bacterial amyloids in neurodegeneration — while they might sometimes drive harmful amyloid formation, they could also potentially counteract the toxicity of host amyloid aggregates.

Funding: The work was supported by the Russian Science Foundation (grant no. 24-26-00124).