Regulation of virulence by butyrate sensing in enterohaemorrhagic Escherichia coli
Regulation of virulence by butyrate sensing in enterohaemorrhagic Escherichia coli
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DOI：
10.1099/mic.0.023499-0
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发表时间：
2009-02-01
期刊：
影响因子：
2.8
通讯作者：
Tobe, Toru
中科院分区：
文献类型：
--
作者：
Nakanishi, Noriko;Tashiro, Kosuke;Tobe, Toru
肠出血性大肠杆菌 (EHEC) 在粘膜表面定植并增殖，引起严重腹泻。由于微生物群的代谢活动，短链脂肪酸 (SCFA) 在肠道中含量丰富，对结肠健康很重要。我们发现，虽然高浓度的 SCFA 抑制了 EHEC 的生长，但在低浓度下，SCFA 显着增强了细胞粘附和诱导附着和消除（A/E）病变所需的毒力基因的表达。在测试的 SCFA 中，丁酸盐即使在 1.25 mM 的低浓度下也能显着增强这些毒力相关基因的表达，但乙酸盐和丙酸盐在浓度高于 40 mM 时仅显示出很小的影响。丁酸盐增强了 LEE1 操纵子的启动子活性，该操纵子编码 LEE 基因的全局调节因子 Ler。这种增强依赖于调节器 PchA。 Irp（亮氨酸响应调节蛋白 Lrp 的基因）的缺失完全消除了丁酸感应。在没有丁酸盐的情况下，Lrp 的组成型活性突变体的表达增强了 LEE 基因的表达，而响应缺陷的 Lrp 衍生物则降低了对丁酸盐的响应。因此，进入远端回肠后，EHEC 可能通过 Lrp 对较高的丁酸盐水平做出反应，增加其毒力表达，从而导致目标生态位的有效定殖。
Enterohaemorrhagic Escherichia coli (EHEC) colonizes and proliferates at the mucosal surface, inducing severe diarrhoea. Short-chain fatty acids (SCFAs) are abundant in the intestine owing to the metabolic activity of microflora, and are important for colonic health. We found that, although a high concentration of SCFAs inhibited the growth of EHEC, at low concentrations, the SCFAs markedly enhanced the expression of the virulence genes required for cell adherence and the induction of attaching and effacing (A/E) lesions. Of the SCFAs tested, butyrate markedly enhanced the expression of these virulence-associated genes, even at the low concentration of 1.25 mM, but acetate and propionate showed only a small effect at concentrations higher than 40 mM. Butyrate enhanced the promoter activity of the LEE1 operon, which encodes a global regulator of the LEE genes, Ler. This enhancement was dependent on a regulator, PchA. Butyrate sensing was completely abrogated by the deletion of Irp, the gene for the leucine-responsive regulatory protein, Lrp. Expression of a constitutively active mutant of Lrp enhanced the expression of the LEE genes in the absence of butyrate, and a response-defective Lrp derivative reduced the response to butyrate. Thus, upon entering the distal ileum, EHEC may respond to the higher butyrate level via Lrp, by increasing its virulence expression, leading to efficient colonization of the target niche.