Genomic analysis reveals that Pseudomonas aeruginosa virulence is combinatorial.
Genomic analysis reveals that Pseudomonas aeruginosa virulence is combinatorial.
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基因组分析表明，铜绿假单胞菌的毒力是组合。
DOI：
10.1186/gb-2006-7-10-r90
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发表时间：
2006
期刊：
影响因子：
12.3
通讯作者：
Ausubel FM
中科院分区：
文献类型：
--
作者：
Lee DG;Urbach JM;Wu G;Liberati NT;Feinbaum RL;Miyata S;Diggins LT;He J;Saucier M;Déziel E;Friedman L;Li L;Grills G;Montgomery K;Kucherlapati R;Rahme LG;Ausubel FM
对高毒力铜绿假单胞菌菌株的测序，并与先前测序的低致病性菌株进行比较，以及在秀丽隐杆线虫模型中的实验测试表明，假单胞菌的毒力是多因素和组合的。铜绿假单胞菌是一种普遍存在的环境细菌，也是重要的机会致病菌。一般来说，以致病性岛的形式获得基因将致病性分离物与非致病性分离物区分开来。因此，我们对铜绿假单胞菌（P. aeruginosa）的高毒力菌株PA14进行了测序，并将其与先前测序的（致病性较低的）菌株pa01进行了比较，以鉴定新的毒力基因。PA14和PAO1基因组非常相似，尽管PA14的基因组（6.5 Mb）略大于PAO1 （6.3 Mb）。在秀丽隐杆线虫致病性模型中，我们鉴定了PAO1中缺失的58个PA14基因簇，以确定这些基因中的哪一个（如果有的话）有助于其增强毒力。首先，我们在秀丽隐杆线虫模型中测试了另外18种不同的菌株，并观察到广泛的致病潜力；然而，使用定制芯片对这些菌株进行基因分型显示，PAO1中缺失的PA14基因的存在与这些菌株的毒力无关。其次，我们利用PA14的全基因组非冗余突变文库鉴定了秀丽隐杆线虫杀伤所需的5个基因（PAO1中缺失）。令人惊讶的是，尽管这五个基因存在于许多其他铜绿假单胞菌菌株中，但它们与秀丽隐杆线虫的毒力无关。一株铜绿假单胞菌致病性所需的基因对其他菌株的毒力既不需要也不预测。因此，我们认为这种生物的毒力是多因素和组合的，是不同遗传背景下一系列致病性相关基因以不同组合相互作用的结果。
Sequencing of a highly virulent strain of Pseudomonas aeruginosa and comparison to a previously sequenced, less pathogenic, strain, together with experimental testing in a C. elegans model, suggests that Pseudomonas virulence is multifactorial and combinatorial. Pseudomonas aeruginosa is a ubiquitous environmental bacterium and an important opportunistic human pathogen. Generally, the acquisition of genes in the form of pathogenicity islands distinguishes pathogenic isolates from nonpathogens. We therefore sequenced a highly virulent strain of P. aeruginosa, PA14, and compared it with a previously sequenced (and less pathogenic) strain, PAO1, to identify novel virulence genes. The PA14 and PAO1 genomes are remarkably similar, although PA14 has a slightly larger genome (6.5 megabses [Mb]) than does PAO1 (6.3 Mb). We identified 58 PA14 gene clusters that are absent in PAO1 to determine which of these genes, if any, contribute to its enhanced virulence in a Caenorhabditis elegans pathogenicity model. First, we tested 18 additional diverse strains in the C. elegans model and observed a wide range of pathogenic potential; however, genotyping these strains using a custom microarray showed that the presence of PA14 genes that are absent in PAO1 did not correlate with the virulence of these strains. Second, we utilized a full-genome nonredundant mutant library of PA14 to identify five genes (absent in PAO1) required for C. elegans killing. Surprisingly, although these five genes are present in many other P. aeruginosa strains, they do not correlate with virulence in C. elegans. Genes required for pathogenicity in one strain of P. aeruginosa are neither required for nor predictive of virulence in other strains. We therefore propose that virulence in this organism is both multifactorial and combinatorial, the result of a pool of pathogenicity-related genes that interact in various combinations in different genetic backgrounds.
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影响因子：
3.1
作者：
Miyata, S;Casey, M;Drenkard, E
通讯作者：
Drenkard, E
影响因子：
56.9
作者：
Kim, DH;Feinbaum, R;Ausubel, FM
通讯作者：
Ausubel, FM
DOI：
10.1089/mcg.2000.5.189
发表时间：
2000-01-01
期刊：
Microbial and Comparative Genomics
影响因子：
--
作者：
Huang, Bixing;Whitchurch, Cynthia B.;Mattick, John S.
通讯作者：
Mattick, John S.
DOI：
10.1073/pnas.052704399
发表时间：
2002-03-05
影响因子：
11.1
作者：
Pukatzki, S;Kessin, RH;Mekalanos, JJ
通讯作者：
Mekalanos, JJ
影响因子：
5.1
作者：
Ernst, RK;D'Argenio, DA;Miller, SI
通讯作者：
Miller, SI