1. Biochemistry and Chemical Biology
  2. Microbiology and Infectious Disease
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Cross-talk between individual phenol soluble modulins in S. aureus biofilm enables rapid and efficient amyloid formation

  1. Masihuz Zaman
  2. Maria Andreasen  Is a corresponding author
  1. Aarhus University, Denmark
Research Article
  • Cited 6
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Cite this article as: eLife 2020;9:e59776 doi: 10.7554/eLife.59776


The infective ability of the opportunistic pathogen Staphylococcus aureus, recognized as the most frequent cause of biofilm-associated infections, is associated with biofilm mediated resistance to host immune response. Phenol-soluble modulins (PSM) comprise the structural scaffold of S. aureus biofilms through self-assembly into functional amyloids, but the role of individual PSMs during biofilm formation remains poorly understood and the molecular pathways of PSM self-assembly have yet to be identified. Here, we demonstrate high degree of cooperation between individual PSMs during functional amyloid formation. PSMα3 initiates the aggregation, forming unstable aggregates capable of seeding other PSMs resulting in stable amyloid structures. Using chemical kinetics we dissect the molecular mechanism of aggregation of individual PSMs showing that PSMα1, PSMα3 and PSMβ1 display secondary nucleation whereas PSMβ2 aggregates through primary nucleation and elongation. Our findings suggest that the various PSMs have solved to ensure fast and efficient biofilm formation through cooperation between individual peptides.

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All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for Figures 1, 2 and 4 in addition to Supplementary Figure 1-5 and 7 and 8.

The following data sets were generated

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Author details

  1. Masihuz Zaman

    Department of Biomedicine, Aarhus University, Aarhus, Denmark
    Competing interests
    The authors declare that no competing interests exist.
  2. Maria Andreasen

    Department of Biomedicine, Aarhus University, Aarhus, Denmark
    For correspondence
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6096-2995


Aarhus Universitets Forskningsfond (AUFF-E-2017-7-16)

  • Maria Andreasen

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Manajit Hayer-Hartl, Max Planck Institute of Biochemistry, Germany

Publication history

  1. Received: June 8, 2020
  2. Accepted: November 30, 2020
  3. Accepted Manuscript published: December 1, 2020 (version 1)
  4. Version of Record published: December 11, 2020 (version 2)


© 2020, Zaman & Andreasen

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.


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