Centre for Biomedical and Health Sciences Research, School of Pharmacy and Biomolecular Sciences, University of Brighton, Lewes Road Brighton, UK.
BMC Genomics. 2010 Jan 19;11:46. doi: 10.1186/1471-2164-11-46.
Little is known regarding the pool of mobile genetic elements associated with the human gut microbiome. In this study we employed the culture independent TRACA system to isolate novel plasmids from the human gut microbiota, and a comparative metagenomic analysis to investigate the distribution and relative abundance of functions encoded by these plasmids in the human gut microbiome.
Novel plasmids were acquired from the human gut microbiome, and homologous nucleotide sequences with high identity (>90%) to two plasmids (pTRACA10 and pTRACA22) were identified in the multiple human gut microbiomes analysed here. However, no homologous nucleotide sequences to these plasmids were identified in the murine gut or environmental metagenomes. Functions encoded by the plasmids pTRACA10 and pTRACA22 were found to be more prevalent in the human gut microbiome when compared to microbial communities from other environments. Among the most prevalent functions identified was a putative RelBE toxin-antitoxin (TA) addiction module, and subsequent analysis revealed that this was most closely related to putative TA modules from gut associated bacteria belonging to the Firmicutes. A broad phylogenetic distribution of RelE toxin genes was observed in gut associated bacterial species (Firmicutes, Bacteroidetes, Actinobacteria and Proteobacteria), but no RelE homologues were identified in gut associated archaeal species. We also provide indirect evidence for the horizontal transfer of these genes between bacterial species belonging to disparate phylogenetic divisions, namely Gram negative Proteobacteria and Gram positive species from the Firmicutes division.
The application of a culture independent system to capture novel plasmids from the human gut mobile metagenome, coupled with subsequent comparative metagenomic analysis, highlighted the unexpected prevalence of plasmid encoded functions in the gut microbial ecosystem. In particular the increased relative abundance and broad phylogenetic distribution was identified for a putative RelBE toxin/antitoxin addiction module, a putative phosphohydrolase/phosphoesterase, and an ORF of unknown function. Our analysis also indicates that some plasmids or plasmid families are present in the gut microbiomes of geographically isolated human hosts with a broad global distribution (America, Japan and Europe), and are potentially unique to the human gut microbiome. Further investigation of the plasmid population associated with the human gut is likely to provide important insights into the development, functioning and evolution of the human gut microbiota.
关于与人类肠道微生物组相关的移动遗传元件库，人们知之甚少。在这项研究中，我们采用了独立于培养的 TRACA 系统从人类肠道微生物群中分离新型质粒，并进行了比较宏基因组分析，以调查这些质粒在人类肠道微生物组中的分布和相对丰度。
从人类肠道微生物群中获得了新型质粒，并在分析的多个人类肠道微生物群中鉴定到与两个质粒（pTRACA10 和 pTRACA22）具有高同源性（>90%）的同源核苷酸序列。然而，在鼠肠道或环境宏基因组中未鉴定到这些质粒的同源核苷酸序列。与来自其他环境的微生物群落相比，质粒 pTRACA10 和 pTRACA22 编码的功能在人类肠道微生物组中更为普遍。鉴定出的最普遍的功能之一是假定的 RelBE 毒素-抗毒素（TA）成瘾模块，随后的分析表明，该模块与来自厚壁菌门的与肠道相关的细菌中假定的 TA 模块最为密切相关。在与肠道相关的细菌物种（厚壁菌门、拟杆菌门、放线菌门和变形菌门）中观察到 RelE 毒素基因的广泛系统发育分布，但在与肠道相关的古菌物种中未鉴定到 RelE 同源物。我们还提供了这些基因在属于不同系统发育分支的细菌物种之间水平转移的间接证据，即革兰氏阴性变形菌和革兰氏阳性厚壁菌门物种。
应用独立于培养的系统从人类肠道移动宏基因组中捕获新型质粒，结合随后的比较宏基因组分析，突出了质粒编码功能在肠道微生物生态系统中出乎意料的普遍性。特别是，鉴定出了假定的 RelBE 毒素/抗毒素成瘾模块、假定的磷酸水解酶/磷酸酯酶和一个未知功能的 ORF 的相对丰度增加和广泛的系统发育分布。我们的分析还表明，一些质粒或质粒家族存在于具有广泛全球分布的地理位置隔离的人类宿主的肠道微生物组中，并且可能是人类肠道微生物组所特有的。进一步研究与人类肠道相关的质粒群体可能为人类肠道微生物组的发展、功能和进化提供重要见解。
