5-Fluorouracil reduces biofilm formation in Escherichia coli K-12 through global regulator AriR as an antivirulence compound

Can Attila, Akihiro Ueda, Thomas K. Wood

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

The uracil analog, 5-fluorouracil (5-FU), reduces virulence and biofilm formation for Pseudomonas aeruginosa PA14 without affecting its growth. As 5-FU is an approved anticancer drug, its antivirulence attributes in P. aeruginosa prompted us to examine the effect of this compound on three different Escherichia coli K-12 strains and its effect on virulence genes in E. coli O157:H7 (EHEC); the mechanism by which it functions was also examined. 5-FU decreased biofilm formation in a dose-dependent manner in E. coli K-12 and repressed the expression of virulence genes in EHEC. Five other uracil analogs were also tested for their effects on biofilm formation, and none of these compounds affected the biofilm formation in E. coli K-12. Whole-transcriptome analysis revealed that 5-FU induced the expression of 157 genes and repressed the expression of 19 genes. Biofilm formation with the addition of 5-FU was checked in 21 isogenic knockout mutants whose gene expression was induced in the microarray data; we found that 5-FU does not decrease biofilm formation of the cells that lack AriR, a global DNA regulator that controls acid resistance in E. coli. Hence, 5-FU represses biofilm formation of E. coli K-12 through AriR and is a novel antivirulence compound for this strain.

Original languageEnglish (US)
Pages (from-to)525-533
Number of pages9
JournalApplied Microbiology and Biotechnology
Volume82
Issue number3
DOIs
StatePublished - Mar 1 2009

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Applied Microbiology and Biotechnology

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