Small-molecule inhibitors target Escherichia coli amyloid biogenesis and biofilm formation
2009 (English)In: Nature Chemical Biology, ISSN 1552-4450, EISSN 1552-4469, Vol. 5, no 12, 913-919 p.Article in journal (Refereed) Published
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
1pili, 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 1pili 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 1pili endows unique anti-biofilm and anti-virulence activities on these compounds.
Place, publisher, year, edition, pages
Nature Publishing Group , 2009. Vol. 5, no 12, 913-919 p.
IdentifiersURN: urn:nbn:se:umu:diva-26861DOI: 10.1038/nchembio.242OAI: oai:DiVA.org:umu-26861DiVA: diva2:274476
Published online 25 October 20092009-10-292009-10-292012-08-10Bibliographically approved