Physical Determinants of Amyloid Assembly in Biofilm Formation

Author:

Andreasen Maria1ORCID,Meisl Georg1,Taylor Jonathan D.2,Michaels Thomas C. T.13,Levin Aviad1,Otzen Daniel E.4,Chapman Matthew R.5,Dobson Christopher M.1,Matthews Steve J.3,Knowles Tuomas P. J.16

Affiliation:

1. Department of Chemistry, University of Cambridge, Cambridge, United Kingdom

2. Department of Life Sciences, Imperial College London, London, United Kingdom

3. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts, USA

4. Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Aarhus, Denmark

5. Department of Molecular, Cellular, and Developmental Biology, University of Michigan College of Literature, Science, and the Arts, Ann Arbor, Michigan, USA

6. Department of Physics, Cavendish Laboratory, Cambridge, United Kingdom

Abstract

Biofilms are generated by bacteria, embedded in the formed extracellular matrix. The biofilm's function is to improve the survival of a bacterial colony through, for example, increased resistance to antibiotics or other environmental stresses. Proteins secreted by the bacteria act as a major structural component of this extracellular matrix, as they self-assemble into highly stable amyloid fibrils, making the biofilm very difficult to degrade by physical and chemical means once formed. By studying the self-assembly mechanism of the fibrils from their monomeric precursors in two unrelated bacteria, our experimental and theoretical approaches shed light on the mechanism of functional amyloid assembly in the context of biofilm formation. Our results suggest that fibril formation may be a rate-limiting step in biofilm formation, which in turn has implications on the protein self-assembly reaction as a target for potential antibiotic drugs.

Funder

The Danish Council for Independent Research

Swiss National ScienceFoundation

Peterhouse College, University of Cambridge

The Danish Council for Independent Reseach

Welcome Trust Senior Investigator Award

Cambridge Center for Misfolding Diseaes

HHS | National Institutes of Health

University of Cambridge | Sidney Sussex College, University of Cambridge

Publisher

American Society for Microbiology

Subject

Virology,Microbiology

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