Control of resistance against bacteriophage killing by a metabolic regulator in meningitis-associated Escherichia coli.
Control of resistance against bacteriophage killing by a metabolic regulator in meningitis-associated Escherichia coli.
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通过代谢调节剂控制脑膜炎相关大肠杆菌对噬菌体杀灭的抵抗力。
DOI：
10.1073/pnas.2210299119
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发表时间：
2022-11-08
影响因子：
11.1
通讯作者：
中科院分区：
文献类型：
--
作者：
细菌基因组经常受到广泛的水平基因转移。基因必须在几个调控水平上进行控制，以确保其编码功能得到适当表达并提供有益的性状。在这里，我们揭示了大肠杆菌转录因子，历史上与窄谱代谢途径，与染色体相互作用的全球和结合DNA在一个不寻常的方式。这些相互作用影响了几个不同过程的调节，包括荚膜多糖的生物发生和修饰。重要的是，后一种功能独立于该调节剂的典型代谢诱导物而发生，并导致对靶向胶囊的噬菌体的杀伤的抗性增强。这项工作强调了特定的调节器可以重新编程，以执行细菌中遥远但关键的功能。细菌中有益于健康的性状是由内在的和水平获得的基因编码的。然而，这些特征并不普遍，细菌基因组的高度镶嵌性需要在转录水平上进行控制以驱动这些过程。已经出现的是，调节灵活性是广泛的大肠杆菌物种，从而预先存在的转录因子可以获得新的和无关的作用，在调节有益的性状。DsdC是E.大肠杆菌中，D-丝氨酸蛋白酶是必需的，并且在新生儿脑膜炎相关的大肠杆菌中通常由两个拷贝编码。大肠杆菌（NMEC）。在这里，我们揭示了DsdC是NMEC中转录的全局调节因子，并且不需要D-丝氨酸来控制新的有益性状。我们发现，DsdC结合染色体在一个不寻常的方式，许多结合位点排列在集群跨越整个操纵子和基因编码序列，如neuO。重要的是，我们确定neuO作为最显着下调的基因在一个菌株中删除两个dsdC拷贝，在存在和不存在的D-丝氨酸。NeuO是在几种NMEC K1分离株中编码的原噬菌体，并介导胶囊O-乙酰化，但对人脑内皮细胞的附着或侵袭没有影响。相反，我们证明了NeuO提供了对K1噬菌体攻击的抗性，并且这种关键功能受DsdC的调节。这项工作强调了如何水平获得酶的功能，在细胞表面的调制可以控制的内在调节提供一个关键的生态效益，以E。大肠杆菌致病型。
Bacterial genomes are often subject to extensive horizontal gene transfer. Genes must be controlled at several levels of regulation to ensure their encoding functions are expressed appropriately and offer beneficial traits. Here, we reveal that an Escherichia coli transcription factor, historically linked to a narrow-spectrum metabolic pathway, interacts with the chromosome globally and by binding to DNA in an unusual fashion. These interactions affect regulation of several distinct processes, including biogenesis and modification of capsular polysaccharide. Importantly, the latter function occurs independently of the canonical metabolic inducer of this regulator and results in enhanced resistance to killing by bacteriophages that target the capsule. This work highlights that specific regulators can be reprogrammed to perform far-removed, yet critical, functions in bacteria. Ecologically beneficial traits in bacteria are encoded by intrinsic and horizontally acquired genes. However, such traits are not universal, and the highly mosaic nature of bacterial genomes requires control at the transcriptional level to drive these processes. It has emerged that regulatory flexibility is widespread in the Escherichia coli species, whereby preexisting transcription factors can acquire new and unrelated roles in regulating beneficial traits. DsdC is the regulator of D-serine tolerance in E. coli, is essential for D-serine catabolism, and is often encoded by two copies in neonatal meningitis–associated E. coli (NMEC). Here, we reveal that DsdC is a global regulator of transcription in NMEC and does not require D-serine for the control of novel beneficial traits. We show that DsdC binds the chromosome in an unusual manner, with many binding sites arranged in clusters spanning entire operons and within gene coding sequences, such as neuO. Importantly, we identify neuO as the most significantly down-regulated gene in a strain deleted for both dsdC copies, in both the presence and absence of D-serine. NeuO is prophage encoded in several NMEC K1 isolates and mediates capsule O-acetylation but has no effect on attachment to or invasion of human brain endothelial cells. Instead, we demonstrate that NeuO provides resistance against K1 bacteriophage attack and that this critical function is regulated by DsdC. This work highlights how a horizontally acquired enzyme that functions in cell-surface modulation can be controlled by an intrinsic regulator to provide a key ecological benefit to an E. coli pathotype.
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DOI：
10.1038/ismej.2014.242
发表时间：
2015-03-17
期刊：
The ISME journal
影响因子：
--
作者：
通讯作者：
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影响因子：
3.1
作者：
HUANG, SH;WASS, C;KIM, KS
通讯作者：
KIM, KS
影响因子：
3.2
作者：
MAAS, WK;DAVIS, BD
通讯作者：
DAVIS, BD
影响因子：
2.8
作者：
Connolly, James P. R.;Turner, Natasha C. A.;O'Boyle, Nicky
通讯作者：
O'Boyle, Nicky
影响因子：
3.2
作者：
Lu, Shuting;Zhang, Xiaobing;Jin, Qi
通讯作者：
Jin, Qi