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

Published

Journal Article

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.

Full Text

Cited Authors

  • Cegelski, L; Pinkner, JS; Hammer, ND; Cusumano, CK; Hung, CS; Chorell, E; Aberg, V; Walker, JN; Seed, PC; Almqvist, F; Chapman, MR; Hultgren, SJ

Published Date

  • December 2009

Published In

Volume / Issue

  • 5 / 12

Start / End Page

  • 913 - 919

PubMed ID

  • 19915538

Pubmed Central ID

  • 19915538

Electronic International Standard Serial Number (EISSN)

  • 1552-4469

Digital Object Identifier (DOI)

  • 10.1038/nchembio.242

Language

  • eng

Conference Location

  • United States