5-Fluorouracil reduces biofilm formation in Escherichia coli K-12 through global regulator AriR as an antivirulence compound
5-Fluorouracil reduces biofilm formation in Escherichia coli K-12 through global regulator AriR as an antivirulence compound
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DOI：
10.1007/s00253-009-1860-8
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发表时间：
2009-03-01
影响因子：
5
通讯作者：
Wood, Thomas K.
中科院分区：
文献类型：
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作者：
Attila, Can;Ueda, Akihiro;Wood, Thomas K.
尿嘧啶类似物5-氟尿嘧啶（5-FU）可以降低铜绿假单胞菌PA14的毒力和生物膜的形成，而不影响其生长。由于5-FU是一种被批准的抗癌药物，其对铜绿假单胞菌的抗毒特性促使我们研究了该化合物对三种不同的大肠杆菌K-12菌株的作用及其对大肠杆菌O157:H7 （EHEC）毒力基因的影响；还研究了它的作用机制。5-FU在大肠杆菌K-12中呈剂量依赖性地减少生物膜的形成，并抑制肠出血性大肠杆菌中毒力基因的表达。另外五种尿嘧啶类似物也测试了它们对生物膜形成的影响，这些化合物都没有影响大肠杆菌K-12的生物膜形成。全转录组分析显示，5-FU诱导157个基因表达，抑制19个基因表达。在基因芯片数据中诱导基因表达的21个等基因敲除突变体中，检测了添加5-FU后生物膜的形成；我们发现5-FU不会减少缺乏AriR的细胞的生物膜形成，AriR是一种控制大肠杆菌耐酸性的全局DNA调节剂。因此，5-FU通过AriR抑制大肠杆菌K-12的生物膜形成，是一种新的抗毒化合物。
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.