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

Cegelski, Lynette (author)
Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, USA.
Pinkner, Jerome S (author)
Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, USA
Hammer, Neal D (author)
Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, Michigan, USA
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Cusumano, Corinne K (author)
Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, USA
Hung, Chia S (author)
Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, USA
Chorell, Erik, 1980- (author)
Umeå universitet,Kemiska institutionen
Åberg, Veronica, 1976- (author)
Umeå universitet,Kemiska institutionen
Walker, Jennifer N (author)
Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, USA
Seed, Patrick C (author)
Departments of Pediatrics and Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, North Carolina, USA
Almqvist, Fredrik (author)
Umeå universitet,Kemiska institutionen
Chapman, Matthew R (author)
Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, Michigan, USA
Hultgren, Scott J (author)
Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, USA
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Department of Molecular Microbiology, Washington University School of Medicine, St Louis, Missouri, USA. Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, USA (creator_code:org_t)
2009-10-25
2009
English.
In: Nature Chemical Biology. - : Nature Publishing Group. - 1552-4450 .- 1552-4469. ; 5:12, s. 913-919
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http://www.nature.co...
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https://urn.kb.se/re...
https://doi.org/10.1...
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  • Journal article (peer-reviewed)
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  • 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 type1pili, 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.

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