Minimization of the Legionella pneumophila genome reveals chromosomal regions involved in host range expansion
Minimization of the Legionella pneumophila genome reveals chromosomal regions involved in host range expansion
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DOI：
10.1073/pnas.1111678108
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发表时间：
2011-09-06
影响因子：
11.1
通讯作者：
Isberg, Ralph R.
中科院分区：
文献类型：
--
作者：
O'Connor, Tamara J.;Adepoju, Yewande;Isberg, Ralph R.
嗜肺军团菌是阿米巴和人类的细菌病原体。细胞内生长需要IVB型分泌系统，其将至少200种不同的蛋白质易位到宿主细胞中。为了区分培养物中生长所必需的蛋白质和细胞内复制所特别需要的蛋白质，进行筛选以鉴定在营养丰富的培养基中最佳生长所必需的基因。这些基因的定位显示，L。嗜肺菌染色体具有由几个大的基因组岛组成的模块化结构，所述基因组岛在细菌学培养物中生长。缺乏这些区域中的六个的菌株，即18.5%的基因组，是可行的，但需要二次点突变以获得最佳生长。这些基因组位点中的五个的同时缺失对细菌在营养丰富的培养基中的生长没有不利影响。值得注意的是，这种最小的基因组菌株，它缺乏31%的已知底物的IVB型系统，导致小鼠巨噬细胞内的细胞内生长的边缘缺陷。与此相反，删除单一区域内阿米巴的增长减少。然而，各个岛屿的重要性在不同的变形虫物种中是不同的。这些基因组岛的宿主特异性要求支持了一个模型，其中外源DNA的获得扩大了L。pneumophila host range.
Legionella pneumophila is a bacterial pathogen of amoebae and humans. Intracellular growth requires a type IVB secretion system that translocates at least 200 different proteins into host cells. To distinguish between proteins necessary for growth in culture and those specifically required for intracellular replication, a screen was performed to identify genes necessary for optimal growth in nutrient-rich medium. Mapping of these genes revealed that the L. pneumophila chromosome has a modular architecture consisting of several large genomic islands that are dispensable for growth in bacteriological culture. Strains lacking six of these regions, and thus 18.5% of the genome, were viable but required secondary point mutations for optimal growth. The simultaneous deletion of five of these genomic loci had no adverse effect on growth of the bacterium in nutrient-rich media. Remarkably, this minimal genome strain, which lacked 31% of the known substrates of the type IVB system, caused only marginal defects in intracellular growth within mouse macrophages. In contrast, deletion of single regions reduced growth within amoebae. The importance of individual islands, however, differed among amoebal species. The host-specific requirements of these genomic islands support a model in which the acquisition of foreign DNA has broadened the L. pneumophila host range.