title: Modulation of curli assembly and pellicle biofilm formation by chemical and protein chaperones.
abstract: Enteric bacteria assemble functional amyloid fibers, curli, on their surfaces that share structural and biochemical properties with disease-associated amyloids. Here, we test rationally designed 2-pyridone compounds for their ability to alter amyloid formation of the major curli subunit CsgA. We identified several compounds that discourage CsgA amyloid formation and several compounds that accelerate CsgA amyloid formation. The ability of inhibitor compounds to stop growing CsgA fibers was compared to the same property of the CsgA chaperone, CsgE. CsgE blocked CsgA amyloid assembly and arrested polymerization when added to actively polymerizing fibers. Additionally, CsgE and the 2-pyridone inhibitors prevented biofilm formation by Escherichia coli at the air-liquid interface of a static culture. We demonstrate that curli amyloid assembly and curli-dependent biofilm formation can be modulated not only by protein chaperones, but also by "chemical chaperones."
authors.affiliation: Umeå Centre for Microbial Research, Umeå University, 901 87 Umeå, Sweden; Department of Chemistry, Umeå University, 901 87 Umeå, Sweden.
authors.forename: Emma K
authors.initials: EK
authors.lastname: Andersson
authors.forename: Christoffer
authors.initials: C
authors.lastname: Bengtsson
authors.forename: Margery L
authors.initials: ML
authors.lastname: Evans
authors.forename: Erik
authors.initials: E
authors.lastname: Chorell
authors.forename: Magnus
authors.initials: M
authors.lastname: Sellstedt
authors.forename: Anders E G
authors.initials: AE
authors.lastname: Lindgren
authors.forename: David A
authors.initials: DA
authors.lastname: Hufnagel
authors.forename: Moumita
authors.initials: M
authors.lastname: Bhattacharya
authors.forename: Peter M
authors.initials: PM
authors.lastname: Tessier
authors.forename: Pernilla
authors.initials: P
authors.lastname: Wittung-Stafshede
authors.forename: Fredrik
authors.initials: F
authors.lastname: Almqvist
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Chapman
mesh_terms: D000682:Amyloid / Q000737:chemistry* / Q000378:metabolism; D018441:Biofilms / Q000187:drug effects* / Q000254:growth & development; D015195:Drug Design; D004926:Escherichia coli / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D007700:Kinetics; D026901:Membrane Transport Proteins / Q000494:pharmacology*; D018832:Molecular Chaperones / Q000494:pharmacology*; D055503:Protein Multimerization / Q000187:drug effects; D017433:Protein Structure, Secondary / Q000187:drug effects; D011728:Pyridones / Q000737:chemistry / Q000494:pharmacology*; D054852:Small Molecule Libraries / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000682:Amyloid; C561979:CsgE protein, E coli; D029968:Escherichia coli Proteins; D026901:Membrane Transport Proteins; D018832:Molecular Chaperones; D011728:Pyridones; D054852:Small Molecule Libraries; C489688:csgA protein, E coli; C017679:2-hydroxypyridine
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