D-serine induces distinct transcriptomes in diverse Escherichia coli pathotypes
D-serine induces distinct transcriptomes in diverse Escherichia coli pathotypes
复制标题
D-丝氨酸在不同的大肠杆菌致病型中诱导不同的转录组
DOI：
10.1101/2021.05.12.443952
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Connolly J
中科院分区：
文献类型：
--
作者：
Connolly J
环境信号的适当解释有助于病原菌的生态位特异性。d-丝氨酸（d-ser）是一种毒性代谢产物，在人体内不同的定植部位存在高度可变的浓度，我们以前发现它能够诱导基因表达的变化。在这项研究中，我们做了惊人的观察，三个大肠杆菌致病型的整体转录反应-肠出血性大肠杆菌。coli（EHEC）、泌尿系致病性E.大肠杆菌（UPEC）和新生儿脑膜炎相关大肠杆菌（E. coli（NMEC）- tod-ser具有高度特异性。事实上，我们没有发现单一的差异表达基因共同的所有三个菌株。我们观察到核糖体相关基因的诱导在肠外病原体UPEC和NMEC，嘌呤代谢基因的诱导在肠道限制性肠出血性大肠杆菌，和UPEC表明不同的转录反应的共同信号。UPEC和NMEC编码dCXA-一个在d-ser存在下解毒和正常生长所需的遗传位点。在积累d-ser的菌株（WT EHEC和缺乏d-ser响应转录激活因子DsdC的UPEC/NMEC突变体）中诱导特异性转录反应，证实了d-ser如果不被代谢则是不利的代谢物的观点。重要的是，许多与UPEC相关的转录组改变与尿转录组的已发表数据相关，支持d-ser传感形成这种病理型尿生态位适应的关键部分的假设。总的来说，我们的研究结果表明不同的多效性反应的一个共同的代谢产物在diverseE。colipathotypes，与生态位选择性的重要影响。
Appropriate interpretation of environmental signals facilitates niche specificity in pathogenic bacteria. However, the responses of niche-specific pathogens to common host signals are poorly understood.d-Serine (d-ser) is a toxic metabolite present in highly variable concentrations at different colonization sites within the human host that we previously found is capable of inducing changes in gene expression. In this study, we made the striking observation that the global transcriptional response of threeEscherichia colipathotypes – enterohaemorrhagicE. coli(EHEC), uropathogenicE. coli(UPEC) and neonatal meningitis-associatedE. coli(NMEC) – tod-ser was highly distinct. In fact, we identified no single differentially expressed gene common to all three strains. We observed the induction of ribosome-associated genes in extraintestinal pathogens UPEC and NMEC only, and the induction of purine metabolism genes in gut-restricted EHEC, and UPEC indicating distinct transcriptional responses to a common signal. UPEC and NMEC encodedsdCXA– a genetic locus required for detoxification and hence normal growth in the presence ofd-ser. Specific transcriptional responses were induced in strains accumulatingd-ser (WT EHEC and UPEC/NMEC mutants lacking thed-ser-responsive transcriptional activator DsdC), corroborating the notion thatd-ser is an unfavourable metabolite if not metabolized. Importantly, many of the UPEC-associated transcriptome alterations correlate with published data on the urinary transcriptome, supporting the hypothesis thatd-ser sensing forms a key part of urinary niche adaptation in this pathotype. Collectively, our results demonstrate distinct pleiotropic responses to a common metabolite in diverseE. colipathotypes, with important implications for niche selectivity.
影响因子：
30.3
作者：
Conover MS;Ruer S;Taganna J;Kalas V;De Greve H;Pinkner JS;Dodson KW;Remaut H;Hultgren SJ
通讯作者：
Hultgren SJ
DOI：
10.1073/pnas.120163297
发表时间：
2000-06-06
影响因子：
11.1
作者：
Datsenko, KA;Wanner, BL
通讯作者：
Wanner, BL