Small-molecule inhibitors target Escherichia coli amyloid biogenesis and biofilm formation

Nat Chem Biol. 2009 Dec;5(12):913-9. doi: 10.1038/nchembio.242. Epub 2009 Oct 25.


Curli are functional extracellular amyloid fibers produced by uropathogenic Escherichia coli (UPEC) and other Enterobacteriaceae. Ring-fused 2-pyridones, such as FN075 and BibC6, inhibited curli biogenesis in UPEC and prevented the in vitro polymerization of the major curli subunit protein CsgA. The curlicides FN075 and BibC6 share a common chemical lineage with other ring-fused 2-pyridones termed pilicides. Pilicides inhibit the assembly of type 1 pili, which are required for pathogenesis during urinary tract infection. Notably, the curlicides retained pilicide activities and inhibited both curli-dependent and type 1-dependent biofilms. Furthermore, pretreatment of UPEC with FN075 significantly attenuated virulence in a mouse model of urinary tract infection. Curli and type 1 pili exhibited exclusive and independent roles in promoting UPEC biofilms, and curli provided a fitness advantage in vivo. Thus, the ability of FN075 to block the biogenesis of both curli and type 1 pili endows unique anti-biofilm and anti-virulence activities on these compounds.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid / antagonists & inhibitors
  • Amyloid / biosynthesis*
  • Animals
  • Bacterial Adhesion / drug effects
  • Bacterial Proteins / antagonists & inhibitors
  • Bacterial Proteins / biosynthesis*
  • Biofilms / growth & development*
  • Escherichia coli Infections / drug therapy
  • Escherichia coli Infections / microbiology
  • Escherichia coli K12 / growth & development
  • Escherichia coli K12 / metabolism
  • Escherichia coli K12 / pathogenicity
  • Escherichia coli Proteins / antagonists & inhibitors
  • Escherichia coli Proteins / biosynthesis*
  • Mice
  • Molecular Structure
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / pharmacology*
  • Small Molecule Libraries / therapeutic use
  • Urinary Tract Infections / drug therapy
  • Urinary Tract Infections / microbiology
  • Uropathogenic Escherichia coli / growth & development
  • Uropathogenic Escherichia coli / metabolism*
  • Uropathogenic Escherichia coli / pathogenicity
  • Virulence


  • Amyloid
  • Bacterial Proteins
  • Escherichia coli Proteins
  • Small Molecule Libraries
  • csgA protein, E coli
  • Crl protein, Bacteria

Associated data

  • PubChem-Substance/85240359
  • PubChem-Substance/85240360
  • PubChem-Substance/85240361
  • PubChem-Substance/85240362