Accelerated Amyloid Beta Pathogenesis by Bacterial Amyloid FapC

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DOI

  • Ibrahim Javed, University of Queensland, Monash Institute of Pharmaceutical Sciences
  • ,
  • Zhenzhen Zhang, Clemson University
  • ,
  • Jozef Adamcik, Swiss Federal Institute of Technology Zurich
  • ,
  • Nicholas Andrikopoulos, Monash Institute of Pharmaceutical Sciences
  • ,
  • Yuhuan Li, Monash Institute of Pharmaceutical Sciences
  • ,
  • Daniel E. Otzen
  • Sijie Lin, Tongji University
  • ,
  • Raffaele Mezzenga, Swiss Federal Institute of Technology Zurich
  • ,
  • Thomas P. Davis, University of Queensland, Monash Institute of Pharmaceutical Sciences
  • ,
  • Feng Ding, Clemson University
  • ,
  • Pu Chun Ke, Monash Institute of Pharmaceutical Sciences, Fudan University

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.

Original languageEnglish
JournalAdvanced Science
DOIs
Publication statusAccepted/In press - 1 Jan 2020

    Research areas

  • amyloid diseases, amyloidosis, brain health cross seeding, gut–brain axis, neurotoxicity

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