D- Serine induces distinct transcriptomes in diverse Escherichia coli pathotypes
D- Serine induces distinct transcriptomes in diverse Escherichia coli pathotypes
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DOI：
10.1099/mic.0.001093
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发表时间：
2021-10-01
期刊：
影响因子：
2.8
通讯作者：
O'Boyle, Nicky
中科院分区：
文献类型：
--
作者：
Connolly, James P. R.;Turner, Natasha C. A.;O'Boyle, Nicky
环境信号的适当解释有助于病原菌的生态位特异性。然而，生态位特异性病原体对常见宿主信号的反应知之甚少。o-丝氨酸（o-ser）是一种毒性代谢物，在人类宿主内的不同定殖位点以高度可变的浓度存在，我们先前发现其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。大肠埃希菌（EHEC）、尿路致病性大肠埃希菌（E.大肠埃希菌（UPEC）和新生儿脑膜炎相关大肠埃希菌（E. coli（NMEC）-对O-ser的特异性较高。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dsdCXA -一个在o-ser存在下解毒并因此正常生长所需的遗传位点。在积累o- ser的菌株（WT EHEC和缺乏o-ser响应性转录激活因子DsdC的UPEC/NMEC突变体）中诱导特异性转录应答，证实了o- ser如果不代谢则是不利的代谢物的观点。重要的是，许多UPEC相关的转录组改变与尿转录组的已发表数据相关，支持以下假设：在这种病理类型中，氧传感形成尿生态位适应的关键部分。总的来说，我们的研究结果表明，不同的E。大肠杆菌致病型，具有重要意义的生态位选择性。
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. o-Serine (o- 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 three Escherichia coli pathotypes - enterohaemorrhagic E. coli (EHEC), uropathogenic E. coli (UPEC) and neonatal meningitis associated E. coli (NMEC) - to o- 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 encode dsdCXA - a genetic locus required for detoxification and hence normal growth in the presence of o- ser. Specific transcriptional responses were induced in strains accumulating o- ser (WT EHEC and UPEC/NMEC mutants lacking the o- ser-responsive transcriptional activator DsdC), corroborating the notion that o- 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 that o- 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 diverse E. coli pathotypes, with important implications for niche selectivity.