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  -