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

  • Genomics and Proteomics
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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.

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Acknowledgements

This research was supported by the NIH (RO1 EB003872) and the ARO (W911NF-06-1-0408).

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Authors and Affiliations

  1. Artie McFerrin Department of Chemical Engineering, Texas A & M University, College Station, TX, 77843-3122, USA

    Can Attila, Akihiro Ueda & Thomas K. Wood

  2. Zachry Department of Civil and Environmental Engineering, Texas A & M University, College Station, TX, 77843-3136, USA

    Thomas K. Wood

  3. Department of Biology, Texas A & M University, College Station, TX, 77843-3258, USA

    Thomas K. Wood

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  1. Can Attila
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  2. Akihiro Ueda
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  3. Thomas K. Wood
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Correspondence to Thomas K. Wood.

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Attila, C., Ueda, A. & Wood, T.K. 5-Fluorouracil reduces biofilm formation in Escherichia coli K-12 through global regulator AriR as an antivirulence compound. Appl Microbiol Biotechnol 82, 525–533 (2009). https://doi.org/10.1007/s00253-009-1860-8

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