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- Title
Small-molecule inhibitors target Escherichia coli amyloid biogenesis and biofilm formation.
- Authors
Cegelski, Lynette; Pinkner, Jerome S.; Hammer, Neal D.; Cusumano, Corinne K.; Hung, Chia S.; Chorell, Erik; Åberg, Veronica; Walker, Jennifer N.; Seed, Patrick C.; Almqvist, Fredrik; Chapman, Matthew R.; Hultgren, Scott J.
- Abstract
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.
- Subjects
ESCHERICHIA coli; ENTEROBACTERIACEAE; AMYLOID; BIOFILMS; PYRIDONE; POLYMERIZATION; URINARY tract infections
- Publication
Nature Chemical Biology, 2009, Vol 5, Issue 12, p913
- ISSN
1552-4450
- Publication type
Article
- DOI
10.1038/nchembio.242