Amyloid-Like β-Aggregates as Force-Sensitive Switches in Fungal Biofilms and Infections

Author:

Lipke Peter N.12ORCID,Klotz Stephen A.3,Dufrene Yves F.4,Jackson Desmond N.1,Garcia-Sherman Melissa C.1ORCID

Affiliation:

1. Department of Biology, Brooklyn College of the City University of New York, Brooklyn, New York, USA

2. The Graduate Center of the City University of New York, New York, New York, USA

3. Division of Infectious Diseases, University of Arizona Health Science Center, Tucson, Arizona, USA

4. Institute of Life Sciences, Université Catholique de Louvain, Louvain-la-Neuve, Belgium

Abstract

SUMMARY Cellular aggregation is an essential step in the formation of biofilms, which promote fungal survival and persistence in hosts. In many of the known yeast cell adhesion proteins, there are amino acid sequences predicted to form amyloid-like β-aggregates. These sequences mediate amyloid formation in vitro. In vivo , these sequences mediate a phase transition from a disordered state to a partially ordered state to create patches of adhesins on the cell surface. These β-aggregated protein patches are called adhesin nanodomains, and their presence greatly increases and strengthens cell-cell interactions in fungal cell aggregation. Nanodomain formation is slow (with molecular response in minutes and the consequences being evident for hours), and strong interactions lead to enhanced biofilm formation. Unique among functional amyloids, fungal adhesin β-aggregation can be triggered by the application of physical shear force, leading to cellular responses to flow-induced stress and the formation of robust biofilms that persist under flow. Bioinformatics analysis suggests that this phenomenon may be widespread. Analysis of fungal abscesses shows the presence of surface amyloids in situ , a finding which supports the idea that phase changes to an amyloid-like state occur in vivo . The amyloid-coated fungi bind the damage-associated molecular pattern receptor serum amyloid P component, and there may be a consequential modulation of innate immune responses to the fungi. Structural data now suggest mechanisms for the force-mediated induction of the phase change. We summarize and discuss evidence that the sequences function as triggers for protein aggregation and subsequent cellular aggregation, both in vitro and in vivo .

Funder

FNRS

HHS | NIH | National Institute of General Medical Sciences

Publisher

American Society for Microbiology

Subject

Molecular Biology,Microbiology,Infectious Diseases

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