title: Between Amyloids and Aggregation Lies a Connection with Strength and Adhesion.
abstract: We tell of a journey that led to discovery of amyloids formed by yeast cell adhesins and their importance in biofilms and host immunity. We begin with the identification of the adhesin functional amyloid-forming sequences that mediate fiber formationin vitro. Atomic force microscopy and confocal microscopy show 2-dimensional amyloid "nanodomains" on the surface of cells that are activated for adhesion. These nanodomains are arrays of adhesin molecules that bind multivalent ligands with high avidity. Nanodomains form when adhesin molecules are stretched in the AFM or under laminar flow. Treatment with antiamyloid perturbants or mutation of the amyloid sequence prevents adhesion nanodomain formation and activation. We are now discovering biological consequences. Adhesin nanodomains promote formation and maintenance of biofilms, which are microbial communities. Also, in abscesses within candidiasis patients, we find adhesin amyloids on the surface of the fungi. In both human infection and aCaenorhabditis elegansinfection model, the presence of fungal surface amyloids elicits anti-inflammatory responses. Thus, this is a story of how fungal adhesins respond to extension forces through formation of cell surface amyloid nanodomains, with key consequences for biofilm formation and host responses.
authors.affiliation: Biology Department, Brooklyn College, The City University of New York, 2900 Bedford Avenue, Brooklyn, NY 11210, USA ; The Graduate Center, The City University of New York, New York, NY 10016, USA.
authors.forename: Peter N
authors.initials: PN
authors.lastname: Lipke
authors.affiliation: Biology Department, Brooklyn College, The City University of New York, 2900 Bedford Avenue, Brooklyn, NY 11210, USA.
authors.forename: Caleen
authors.initials: C
authors.lastname: Ramsook
authors.affiliation: Biology Department, Brooklyn College, The City University of New York, 2900 Bedford Avenue, Brooklyn, NY 11210, USA.
authors.forename: Melissa C
authors.initials: MC
authors.lastname: Garcia-Sherman
authors.affiliation: Biology Department, Brooklyn College, The City University of New York, 2900 Bedford Avenue, Brooklyn, NY 11210, USA.
authors.forename: Desmond N
authors.initials: DN
authors.lastname: Jackson
authors.affiliation: Biology Department, Brooklyn College, The City University of New York, 2900 Bedford Avenue, Brooklyn, NY 11210, USA ; The Graduate Center, The City University of New York, New York, NY 10016, USA.
authors.forename: Cho X J
authors.initials: CX
authors.lastname: Chan
authors.affiliation: Biology Department, Brooklyn College, The City University of New York, 2900 Bedford Avenue, Brooklyn, NY 11210, USA ; The Graduate Center, The City University of New York, New York, NY 10016, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Bois
authors.affiliation: Section of Infectious Diseases, University of Arizona, Tucson, AZ 85724, USA.
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Klotz
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