TY - JOUR
AU - Perov, Sergei
AU - Lidor, Ofir
AU - Salinas, Nir
AU - Golan, Nimrod
AU - Tayeb- Fligelman, Einav
AU - Deshmukh, Maya
AU - Willbold, Dieter
AU - Landau, Meytal
TI - Structural Insights into Curli CsgA Cross-β Fibril Architecture Inspire Repurposing of Anti-amyloid Compounds as Anti-biofilm Agents
JO - PLoS pathogens
VL - 15
IS - 8
SN - 1553-7374
CY - Lawrence, Kan.
PB - PLoS
M1 - FZJ-2020-00230
SP - e1007978 -
PY - 2019
AB - 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
LB - PUB:(DE-HGF)16
C6 - pmid:31469892
UR - <Go to ISI:>//WOS:000488322100029
DO - DOI:10.1371/journal.ppat.1007978
UR - https://juser.fz-juelich.de/record/872752
ER -