Accelerated Amyloid Beta Pathogenesis by Bacterial Amyloid FapC.

Javed I; Zhang Z; Adamcik J; Andrikopoulos N; Li Y; Otzen DE; Lin S; Mezzenga R; Davis TP; Ding F; Ke PC

doi:10.1002/advs.202001299

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Journal article

Accelerated Amyloid Beta Pathogenesis by Bacterial Amyloid FapC.

Javed I Australian Institute for Bioengineering and Nanotechnology University of Queensland Brisbane QLD 4072 Australia.
Zhang Z Department of Physics and Astronomy Clemson University Clemson SC 29634 USA.
Adamcik J Food & Soft Materials Department of Health Science & Technology ETH Zurich Schmelzbergstrasse 9, LFO, E23 Zurich 8092 Switzerland.
Andrikopoulos N ARC Centre of Excellence in Convergent Bio-Nano Science and Technology Monash Institute of Pharmaceutical Sciences Monash University 381 Royal Parade Parkville VIC 3052 Australia.
Li Y ARC Centre of Excellence in Convergent Bio-Nano Science and Technology Monash Institute of Pharmaceutical Sciences Monash University 381 Royal Parade Parkville VIC 3052 Australia.
Otzen DE Interdisciplinary Nanoscience Center (iNANO) University of Aarhus Aarhus C Aarhus 8000 Denmark.
Lin S College of Environmental Science and Engineering Biomedical Multidisciplinary Innovation Research Institute Shanghai East Hospital Shanghai Institute of Pollution Control and Ecological Security Tongji University 1239 Siping Road Shanghai 200092 China.
Mezzenga R Food & Soft Materials Department of Health Science & Technology ETH Zurich Schmelzbergstrasse 9, LFO, E23 Zurich 8092 Switzerland.
Davis TP Australian Institute for Bioengineering and Nanotechnology University of Queensland Brisbane QLD 4072 Australia.
Ding F Department of Physics and Astronomy Clemson University Clemson SC 29634 USA.
Ke PC ARC Centre of Excellence in Convergent Bio-Nano Science and Technology Monash Institute of Pharmaceutical Sciences Monash University 381 Royal Parade Parkville VIC 3052 Australia.

2020-10-01

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Advanced science (Weinheim, Baden-Wurttemberg, Germany). - 2020

English The gut-brain axis has attracted increasing attention in recent years, fueled by accumulating symptomatic, physiological, and pathological findings. In this study, the aggregation and toxicity of amyloid beta (Aβ), the pathogenic peptide associated with Alzheimer's disease (AD), seeded by FapC amyloid fragments (FapCS) of Pseudomonas aeruginosa that colonizes the gut microbiome through infections are examined. FapCS display favorable binding with Aβ and a catalytic capacity in seeding the peptide amyloidosis. Upon seeding, twisted Aβ fibrils assume a much-shortened periodicity approximating that of FapC fibrils, accompanied by a 37% sharp rise in the fibrillar diameter, compared with the control. The robust seeding capacity for Aβ by FapCS and the biofilm fragments derived from P. aeruginosa entail abnormal behavior pathology and immunohistology, as well as impaired cognitive function of zebrafish. Together, the data offer the first concrete evidence of structural integration and inheritance in peptide cross-seeding, a crucial knowledge gap in understanding the pathological correlations between different amyloid diseases. The catalytic role of infectious bacteria in promoting Aβ amyloidosis may be exploited as a potential therapeutic target, while the altered mesoscopic signatures of Aβ fibrils may serve as a prototype for molecular assembly and a biomarker for screening bacterial infections in AD.

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