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Evaluative Profiling of Arsenic Sensing and Regulatory Systems in the Human Microbiome Project Genomes

机译:评估人类微生物组项目基因组中的砷传感和调控系统

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The influence of environmental chemicals including arsenic, a type 1 carcinogen, on the composition and function of the human-associated microbiota is of significance in human health and disease. We have developed a suite of bioinformatics and visual analytics methods to evaluate the availability (presence or absence) and abundance of functional annotations in a microbial genome for seven Pfam protein families: As(III)-responsive transcriptional repressor (ArsR), anion-transporting ATPase (ArsA), arsenical pump membrane protein (ArsB), arsenate reductase (ArsC), arsenical resistance operon transacting repressor (ArsD), water/glycerol transport protein (aquaporins), and universal stress protein (USP). These genes encode function for sensing and/or regulating arsenic content in the bacterial cell. The evaluative profiling strategy was applied to 3,274 genomes from which 62 genomes from 18 genera were identified to contain genes for the seven protein families. Our list included 12 genomes in the Human Microbiome Project (HMP) from the following genera: Citrobacter, Escherichia, Lactobacillus, Providencia, Rhodococcus, and Staphylococcus. Gene neighborhood analysis of the arsenic resistance operon in the genome of Bacteroides thetaiotaomicron VPI-5482, a human gut symbiont, revealed the adjacent arrangement of genes for arsenite binding/transfer (ArsD) and cytochrome c biosynthesis (DsbD_2). Visual analytics facilitated evaluation of protein annotations in 367 genomes in the phylum Bacteroidetes identified multiple genomes in which genes for ArsD and DsbD_2 were adjacently arranged. Cytochrome c, produced by a posttranslational process, consists of heme-containing proteins important for cellular energy production and signaling. Further research is desired to elucidate arsenic resistance and arsenic-mediated cellular energy production in the Bacteroidetes.
机译:包括砷(一种1型致癌物)在内的环境化学物质对人类相关微生物群的组成和功能的影响在人类健康和疾病中具有重要意义。我们已经开发了一套生物信息学和视觉分析方法来评估七个Pfam蛋白家族在微生物基因组中的功能性注释的存在(有无)和丰富度:As(III)反应型转录抑制因子(ArsR),阴离子转运ATPase(ArsA),砷泵蛋白(ArsB),砷酸盐还原酶(ArsC),砷抗操纵子操纵子阻遏物(ArsD),水/甘油转运蛋白(aquaporins)和通用应激蛋白(USP)。这些基因编码用于感测和/或调节细菌细胞中砷含量的功能。评估分析策略应用于3274个基因组,从中鉴定出18个属的62个基因组包含7个蛋白质家族的基因。我们的清单包括来自以下属的人类微生物组计划(HMP)中的12个基因组:柠檬酸杆菌,大肠杆菌,乳杆菌,普罗维登西亚,红球菌和葡萄球菌。人类肠道共生细菌拟杆菌(Theactotaides thetaiotaomicron VPI-5482)基因组中砷抗性操纵子的基因邻域分析揭示了砷结合/转移(ArsD)和细胞色素c生物合成(DsbD_2)的相邻基因排列。视觉分析有助于评估门菌中367个基因组中的蛋白质注释,从而鉴定出多个基因组,其中ArsD和DsbD_2的基因相邻排列。由翻译后过程产生的细胞色素c由对细胞能量产生和信号转导很重要的含血红素的蛋白质组成。希望有进一步的研究来阐明拟杆菌中的砷抗性和砷介导的细胞能量产生。

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