When and where? Pathogenic Escherichia coli differentially sense host D-serine using a universal transporter system to monitor their environment.
When and where? Pathogenic Escherichia coli differentially sense host D-serine using a universal transporter system to monitor their environment.
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DOI：
10.15698/mic2016.04.494
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发表时间：
2016-03-31
期刊：
影响因子：
--
通讯作者：
Roe AJ
中科院分区：
文献类型：
--
作者：
Connolly JP;Roe AJ
当细菌面临宿主体内的多种逆境时，感知环境刺激至关重要。对这些信号做出适当的反应，然后将这些反应整合到细胞的调节网络中，使细菌能够精确控制它们应该建立定殖的时间和地点。 D-丝氨酸是人类尿道中丰富的代谢物，但对于缺乏 D-丝氨酸耐受位点的大肠杆菌来说是一种有毒代谢物。因此，肠出血性大肠杆菌 (EHEC) 无法分解代谢 D-丝氨酸，并专门定植于大肠（D-丝氨酸含量较低的环境）。然而，EHEC 可以使用 D-丝氨酸感应来抑制定植，从而发出不利环境存在的信号。在我们最近的工作中（Connolly, et al. PLoS Pathogens (2016) 12(1): e1005359），我们描述了在大肠杆菌中发现的功能性且先前未表征的 D-丝氨酸摄取系统。所鉴定的基因在所有大肠杆菌谱系中高度保守，但在独特的致病背景中受到差异性调节。研究发现，与直觉相反，EHEC 会增加 D-丝氨酸的摄取，但这是一个可耐受的过程，可用于增加对此信号的转录反应。研究还发现，该系统已整合到肠出血性大肠杆菌特异性毒力基因的转录网络中，证明核心基因组成分具有重要的病型特异性适应性。
Sensing environmental stimuli is critically important for bacteria when faced with the multitude of adversities presented within the host. Responding appropriately to these signals and in turn integrating these responses into the regulatory network of the cell allows bacteria to control precisely when and where they should establish colonization. D-serine is an abundant metabolite of the human urinary tract but is a toxic metabolite for Escherichia coli that lack a D-serine tolerance locus. Enterohaemorrhagic E. coli (EHEC) cannot catabolize D-serine for this reason and colonize the large intestine specifically, an environment low in D-serine. EHEC can however use D-serine sensing to repress colonization thus signaling the presence of an unfavorable environment. In our recent work (Connolly, et al. PLoS Pathogens (2016) 12(1): e1005359), we describe the discovery of a functional and previously uncharacterized D-serine uptake system in E. coli. The genes identified are highly conserved in all E. coli lineages but are regulated differentially in unique pathogenic backgrounds. The study identified that EHEC, counter-intuitively, increase D-serine uptake in its presence but that this is a tolerated process and is used to increase the transcriptional response to this signal. It was also found that the system has been integrated into the transcriptional network of EHEC-specific virulence genes, demonstrating an important pathotype-specific adaptation of core genome components.