umu.sePublikationer
Ändra sökning
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Pilicide ec240 Disrupts Virulence Circuits in Uropathogenic Escherichia coli
Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
Visa övriga samt affilieringar
2014 (Engelska)Ingår i: mBio, ISSN 2161-2129, E-ISSN 2150-7511, Vol. 5, nr 6, s. UNSP e02038-Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Chaperone-usher pathway (CUP) pili are extracellular organelles produced by Gram-negative bacteria that mediate bacterial pathogenesis. Small-molecule inhibitors of CUP pili, termed pilicides, were rationally designed and shown to inhibit type 1 or P piliation. Here, we show that pilicide ec240 decreased the levels of type 1, P, and S piliation. Transcriptomic and proteomic analyses using the cystitis isolate UTI89 revealed that ec240 dysregulated CUP pili and decreased motility. Paradoxically, the transcript levels of P and S pilus genes were increased during growth in ec240, even though the level of P and S piliation decreased. In contrast, the most downregulated transcripts after growth in ec240 were from the type 1 pilus genes. Type 1 pilus expression is controlled by inversion of the fimS promoter element, which can oscillate between phase on and phase off orientations. ec240 induced the fimS phase off orientation, and this effect was necessary for the majority of ec240's inhibition of type 1 piliation. ec240 increased levels of the transcriptional regulators SfaB and PapB, which were shown to induce the fimS promoter phase off orientation. Furthermore, the effect of ec240 on motility was abolished in the absence of the SfaB, PapB, SfaX, and PapX regulators. In contrast to the effects of ec240, deletion of the type 1 pilus operon led to increased S and P piliation and motility. Thus, ec240 dysregulated several uropathogenic Escherichia coli (UPEC) virulence factors through different mechanisms and independent of its effects on type 1 pilus biogenesis and may have potential as an antivirulence compound. IMPORTANCE CUP pili and flagella play active roles in the pathogenesis of a variety of Gram-negative bacterial infections, including urinary tract infections mediated by UPEC. These are extremely common infections that are often recurrent and increasingly caused by antibiotic-resistant organisms. Preventing piliation and motility through altered regulation and assembly of these important virulence factors could aid in the development of novel therapeutics. This study increases our understanding of the regulation of these virulence factors, providing new avenues by which to target their expression.

Ort, förlag, år, upplaga, sidor
2014. Vol. 5, nr 6, s. UNSP e02038-
Nationell ämneskategori
Organisk kemi Mikrobiologi inom det medicinska området
Identifikatorer
URN: urn:nbn:se:umu:diva-99393DOI: 10.1128/mBio.02038-14ISI: 000347073600033OAI: oai:DiVA.org:umu-99393DiVA, id: diva2:788698
Tillgänglig från: 2015-02-16 Skapad: 2015-02-07 Senast uppdaterad: 2018-06-07Bibliografiskt granskad

Open Access i DiVA

fulltext(5734 kB)175 nedladdningar
Filinformation
Filnamn FULLTEXT01.pdfFilstorlek 5734 kBChecksumma SHA-512
934dd507a06b4fcfb98f2dc695db5ad904afa69951d2eab4682ce726f7ec12e1e1b4b6f0cc1bb8fc43399b3affebf396b304ad069fcabc5e4cdb21867e4845c3
Typ fulltextMimetyp application/pdf

Övriga länkar

Förlagets fulltext

Personposter BETA

Chorell, ErikAlmqvist, Fredrik

Sök vidare i DiVA

Av författaren/redaktören
Chorell, ErikAlmqvist, Fredrik
Av organisationen
Kemiska institutionenUmeå Centre for Microbial Research (UCMR)
I samma tidskrift
mBio
Organisk kemiMikrobiologi inom det medicinska området

Sök vidare utanför DiVA

GoogleGoogle Scholar
Totalt: 175 nedladdningar
Antalet nedladdningar är summan av nedladdningar för alla fulltexter. Det kan inkludera t.ex tidigare versioner som nu inte längre är tillgängliga.

doi
urn-nbn

Altmetricpoäng

doi
urn-nbn
Totalt: 396 träffar
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf