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系统的系统发育和转录组学分析揭示了 中 c-di-GMP 基础水平所需的二鸟苷酸环化酶和磷酸二酯酶。

Diguanylate Cyclases and Phosphodiesterases Required for Basal-Level c-di-GMP in as Revealed by Systematic Phylogenetic and Transcriptomic Analyses.

机构信息

State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.

Institut National de la Recherche Agronomique, Université François Rabelais de Tours, UMR 1282, Nouzilly, France.

出版信息

Appl Environ Microbiol. 2019 Oct 16;85(21). doi: 10.1128/AEM.01194-19. Print 2019 Nov 1.

Abstract

Cyclic diguanosine monophosphate (c-di-GMP) is an important second messenger involved in bacterial switching from motile to sessile lifestyles. In the opportunistic pathogen , at least 40 genes are predicted to encode proteins for the making and breaking of this signal molecule. However, there is still paucity of information concerning the systemic expression pattern of these genes and the functions of uncharacterized genes. In this study, we analyzed the phylogenetic distribution of genes from that were predicted to have a GGDEF domain and found five genes (PA5487, PA0285, PA0290, PA4367, and PA5017) with highly conserved distribution across 52 public complete pseudomonad genomes. PA5487 was further characterized as a typical diguanylate cyclase (DGC) and was named A systemic analysis of the gene expression data revealed that the expression of is highly invariable and that probably functions as a conserved gene to maintain the basal level of c-di-GMP, as reinforced by gene expression analyses. The other four conserved genes also had an expression pattern similar to that of The functional analysis suggested that PA0290 encoded a DGC, while the others functioned as phosphodiesterases (PDEs). Our data revealed that there are five DGC and PDE genes that maintain the basal level of c-di-GMP in is an opportunistic pathogen that can cause infections in animals, humans, and plants. The formation of biofilms by is the central mode of action to persist in hosts and evade immune and antibiotic attacks. Cyclic-di-GMP (c-di-GMP) is an important second messenger involved in the regulation of biofilm formation. In PAO1 strain, there are around 40 genes that encode enzymes for making and breaking this dinucleotide. A major missing piece of information in this field is the phylogeny and expression profile of those genes. Here, we took a systemic approach to investigate this mystery. We found that among 40 c-di-GMP metabolizing genes, 5 have well-conserved phylogenetic distribution and invariable expression profiles, suggesting that there are enzymes required for the basal level of c-di-GMP in This study thus provides putative therapeutic targets against infections.

摘要

环二鸟苷酸(c-di-GMP)是一种重要的第二信使,参与细菌从运动状态到静止状态的转换。在机会致病菌中,至少有 40 个基因被预测编码这种信号分子的合成和分解蛋白。然而,关于这些基因的系统表达模式以及未鉴定基因的功能,我们仍然知之甚少。在这项研究中,我们分析了 中具有 GGDEF 结构域的基因的系统发育分布,发现了 5 个基因(PA5487、PA0285、PA0290、PA4367 和 PA5017)在 52 个公共全假单胞菌基因组中具有高度保守的分布。PA5487 进一步被鉴定为典型的双鸟苷酸环化酶(DGC),并被命名为 对基因表达数据的系统分析表明, 的表达高度不变,可能作为一个保守基因发挥作用,维持 c-di-GMP 的基础水平,这一点通过基因表达分析得到了加强。其他四个保守基因的表达模式也与 相似。功能分析表明,PA0290 编码一个 DGC,而其他基因则作为磷酸二酯酶(PDE)发挥作用。我们的数据表明, 中有五个 DGC 和 PDE 基因维持 c-di-GMP 的基础水平, 是一种机会致病菌,可以引起动物、人类和植物的感染。 形成生物膜是其在宿主中持续存在并逃避免疫和抗生素攻击的主要作用模式。环二鸟苷酸(c-di-GMP)是一种重要的第二信使,参与生物膜形成的调控。在 PAO1 菌株中,大约有 40 个基因编码合成和分解这个二核苷酸的酶。在这个领域,一个主要的缺失信息是这些基因的系统发育和表达谱。在这里,我们采用系统的方法来研究这个奥秘。我们发现,在 40 个 c-di-GMP 代谢基因中,有 5 个具有很好的系统发育分布和不变的表达模式,这表明 中存在维持 c-di-GMP 基础水平所必需的酶。因此,这项研究为针对 感染提供了潜在的治疗靶点。

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