Microbial Adhesion Group, DTU Food, Bldg. 204, Technical University of Denmark, 2800 Lyngby, Denmark.
Mol Genet Genomics. 2010 Dec;284(6):437-54. doi: 10.1007/s00438-010-0578-8. Epub 2010 Oct 1.
Strain CFT073 is a bona fide uropathogen, whereas strains 83972 and Nissle 1917 are harmless probiotic strains of urinary tract and faecal origin, respectively. Despite their different environmental origins and dispositions the three strains are very closely related and the ancestors of 83972 and Nissle 1917 must have been very similar to CFT073. Here, we report the first functional genome profiling of Nissle 1917 and the first biofilm profiling of a uropathogen. Transcriptomic profiling revealed that Nissle 1917 expressed many UPEC-associated genes and showed that the active genomic profiles of the three strains are closely related. The data demonstrate that the distance from a pathogen to a probiotic strain can be surprisingly short. We demonstrate that Nissle 1917, in spite of its intestinal niche origin, grows well in urine, and is a good biofilm former in this medium in which it also out-competes CFT073 during planktonic growth. The role in biofilm formation of three up-regulated genes, yhaK, yhcN and ybiJ, was confirmed by knockout mutants in Nissle 1917 and CFT073. Two of these mutants CFT073∆yhcN and CFT073∆ybiJ had significantly reduced motility compared with the parent strain, arguably accounting for the impaired biofilm formation. Although the three strains have very different strategies vis-à-vis the human host their functional gene profiles are surprisingly similar. It is also interesting to note that the only two Escherichia coli strains used as probiotics are in fact deconstructed pathogens.
菌株 CFT073 是一种真正的尿路病原体,而菌株 83972 和 Nissle 1917 分别是尿路和肠道来源的无害益生菌株。尽管它们的环境来源和特性不同,但这三种菌株非常密切相关,83972 和 Nissle 1917 的祖先一定与 CFT073 非常相似。在这里,我们报告了 Nissle 1917 的第一个功能基因组图谱和尿路病原体的第一个生物膜图谱。转录组学分析表明,Nissle 1917 表达了许多 UPEC 相关基因,并表明三种菌株的活跃基因组图谱密切相关。这些数据表明,从病原体到益生菌株的距离可能出人意料地近。我们证明,尽管 Nissle 1917 起源于肠道,但它在尿液中生长良好,并且在该培养基中也是一种良好的生物膜形成菌,在浮游生长中它也能与 CFT073 竞争。通过 Nissle 1917 和 CFT073 的敲除突变体证实了三个上调基因 yhaK、yhcN 和 ybiJ 在生物膜形成中的作用。这三个突变体 CFT073ΔyhcN 和 CFT073ΔybiJ 的运动性与亲本菌株相比明显降低,这可以解释生物膜形成受损的原因。尽管这三种菌株对人类宿主有非常不同的策略,但它们的功能基因图谱惊人地相似。值得注意的是,用作益生菌的两种大肠杆菌菌株实际上是被解构的病原体。