Life on arginine for Mycoplasma hominis: clues from its minimal genome and comparison with other human urogenital mycoplasmas.
Life on arginine for Mycoplasma hominis: clues from its minimal genome and comparison with other human urogenital mycoplasmas.
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DOI：
10.1371/journal.pgen.1000677
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发表时间：
2009-10
期刊：
影响因子：
4.5
通讯作者：
Bébéar C
中科院分区：
文献类型：
--
作者：
Pereyre S;Sirand-Pugnet P;Beven L;Charron A;Renaudin H;Barré A;Avenaud P;Jacob D;Couloux A;Barbe V;de Daruvar A;Blanchard A;Bébéar C
人型支原体是一种机会性的人型支原体。另外两个致病的人类物种，生殖支原体和微小解脲支原体，与人支原体居住在同一个自然生态位中：泌尿生殖道。这三个物种具有重叠但不同的致病作用。它们的基因组最小，因此代谢能力降低，其特征是不同的能量生成途径。对人分枝杆菌PG21基因组序列的分析表明，它是自复制自由生物中第二小的基因组(665,445个碱基，537个编码序列(CDS))。预测了5组基因在人型支原体和系统发育上较远的微小支原体之间的水平基因转移(HGT)。我们根据预测的基因重建了人型支原体的代谢途径，特别强调了能量产生的途径。Embden-Meyerhoff-Parns途径是不完整的，没有一个单一的酶。我们鉴定了构成精氨酸二水解酶途径的三种蛋白质。这一途径被发现对促进体内生长是必不可少的。预测的二甲基精氨酸二甲氨基水解酶的存在表明精氨酸分解代谢比最初描述的更复杂。这种酶可能是由HGT从非摩尔细菌中获得的。三个最小分子量基因组的比较表明，247个CDSS是三个基因组共有的，220个CDSS是人型支原体所特有的，172个CDSS是生殖支原体所特有的，280个CDSS是微小支原体所特有的。在这些物种特有的基因中，可以识别出两组主要的基因：一组包括参与各种能量产生途径的基因，取决于所使用的能源(葡萄糖、尿素或精氨酸)；另一组涉及细胞黏附和毒力。因此，可以设想一个最小的支原体细胞，不包括细胞黏附和毒力相关基因，包含一个核心基因组(247个基因)，外加一组提供能量所需的基因。对于人型支原体来说，这个集合将包括247+9个基因，从而导致理论上最小的基因组由256个基因组成。人型支原体、生殖支原体和微小解脲支原体是人类的致病细菌，它们定植于泌尿生殖道。它们的基因组最小，因此具有最低的新陈代谢能力。然而，它们有不同的能量产生途径和不同的致病作用。我们比较了这三个人类病原体最小物种的基因组，进一步洞察了假设的生命所需的最小基因组的组成。为此，我们对人型支原体的整个基因组进行了测序，并根据基因预测重建了它的能量生成途径。其不同寻常的主要能量产生途径通过精氨酸水解在基因组分析和体内分析中都得到了证实。我们的发现表明，人型支原体和微小支原体经历了基因交换，可能是在共享共同宿主的情况下进行的。我们提出了一组可能代表最小基因组的基因。对于人分枝杆菌来说，这个最小的基因组，不包括细胞黏附和毒力相关基因，可以定义为包括三种最小的生殖器软体动物共有的247个基因，以及一组为细胞新陈代谢产生能量所需的9个基因。这项研究为人工基因组的合成提供了新的思路。
Mycoplasma hominis is an opportunistic human mycoplasma. Two other pathogenic human species, M. genitalium and Ureaplasma parvum, reside within the same natural niche as M. hominis: the urogenital tract. These three species have overlapping, but distinct, pathogenic roles. They have minimal genomes and, thus, reduced metabolic capabilities characterized by distinct energy-generating pathways. Analysis of the M. hominis PG21 genome sequence revealed that it is the second smallest genome among self-replicating free living organisms (665,445 bp, 537 coding sequences (CDSs)). Five clusters of genes were predicted to have undergone horizontal gene transfer (HGT) between M. hominis and the phylogenetically distant U. parvum species. We reconstructed M. hominis metabolic pathways from the predicted genes, with particular emphasis on energy-generating pathways. The Embden–Meyerhoff–Parnas pathway was incomplete, with a single enzyme absent. We identified the three proteins constituting the arginine dihydrolase pathway. This pathway was found essential to promote growth in vivo. The predicted presence of dimethylarginine dimethylaminohydrolase suggested that arginine catabolism is more complex than initially described. This enzyme may have been acquired by HGT from non-mollicute bacteria. Comparison of the three minimal mollicute genomes showed that 247 CDSs were common to all three genomes, whereas 220 CDSs were specific to M. hominis, 172 CDSs were specific to M. genitalium, and 280 CDSs were specific to U. parvum. Within these species-specific genes, two major sets of genes could be identified: one including genes involved in various energy-generating pathways, depending on the energy source used (glucose, urea, or arginine) and another involved in cytadherence and virulence. Therefore, a minimal mycoplasma cell, not including cytadherence and virulence-related genes, could be envisaged containing a core genome (247 genes), plus a set of genes required for providing energy. For M. hominis, this set would include 247+9 genes, resulting in a theoretical minimal genome of 256 genes. Mycoplasma hominis, M. genitalium, and Ureaplasma parvum are human pathogenic bacteria that colonize the urogenital tract. They have minimal genomes, and thus have a minimal metabolic capacity. However, they have distinct energy-generating pathways and distinct pathogenic roles. We compared the genomes of these three human pathogen minimal species, providing further insight into the composition of hypothetical minimal gene sets needed for life. To this end, we sequenced the whole M. hominis genome and reconstructed its energy-generating pathways from gene predictions. Its unusual major energy-producing pathway through arginine hydrolysis was confirmed in both genome analyses and in vivo assays. Our findings suggest that M. hominis and U. parvum underwent genetic exchange, probably while sharing a common host. We proposed a set of genes likely to represent a minimal genome. For M. hominis, this minimal genome, not including cytadherence and virulence-related genes, can be defined comprising the 247 genes shared by the three minimal genital mollicutes, combined with a set of nine genes needed for energy production for cell metabolism. This study provides insight for the synthesis of artificial genomes.
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影响因子：
3.2
作者：
Dhandayuthapani, S;Blaylock, MW;Baseman, JB
通讯作者：
Baseman, JB
影响因子：
3.2
作者：
Henrich, B;Hopfe, M;Hadding, U
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Hadding, U
DOI：
10.1165/ajrcmb.19.6.2904
发表时间：
1998-12-01
影响因子：
6.4
作者：
Dowling, RB;Newton, R;Wilson, R
通讯作者：
Wilson, R
影响因子：
3.2
作者：
FENSKE, JD;KENNY, GE
通讯作者：
KENNY, GE
影响因子：
56.9
作者：
FRASER, CM;GOCAYNE, JD;VENTER, JC
通讯作者：
VENTER, JC