%0 Journal Article
%A Perov, Sergei
%A Lidor, Ofir
%A Salinas, Nir
%A Golan, Nimrod
%A Tayeb- Fligelman, Einav
%A Deshmukh, Maya
%A Willbold, Dieter
%A Landau, Meytal
%T Structural Insights into Curli CsgA Cross-β Fibril Architecture Inspire Repurposing of Anti-amyloid Compounds as Anti-biofilm Agents
%J PLoS pathogens
%V 15
%N 8
%@ 1553-7374
%C Lawrence, Kan.
%I PLoS
%M FZJ-2020-00230
%P e1007978 -
%D 2019
%X Curli amyloid fibrils secreted by Enterobacteriaceae mediate host cell adhesion and contribute to biofilm formation, thereby promoting bacterial resistance to environmental stressors. Here, we present crystal structures of amyloid-forming segments from the major curli subunit, CsgA, revealing steric zipper fibrils of tightly mated β-sheets, demonstrating a structural link between curli and human pathological amyloids. D-enantiomeric peptides, originally developed to interfere with Alzheimer's disease-associated amyloid-β, inhibited CsgA fibrillation and reduced biofilm formation in Salmonella typhimurium. Moreover, as previously shown, CsgA fibrils cross-seeded fibrillation of amyloid-β, providing support for the proposed structural resemblance and potential for cross-species amyloid interactions. The presented findings provide structural insights into amyloidogenic regions important for curli formation, suggest a novel strategy for disrupting amyloid-structured biofilms, and hypothesize on the formation of self-propagating prion-like species originating from a microbial source that could influence neurodegenerative diseases
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:31469892
%U <Go to ISI:>//WOS:000488322100029
%R 10.1371/journal.ppat.1007978
%U https://juser.fz-juelich.de/record/872752