PLoS Patho：全基因组水平揭示绿脓杆菌毒力相关的基因

近日，刊登在国际著名杂志<em>PLoS Pathogens</em>上的一篇研究报告“Genome-Wide Identification of Pseudomonas aeruginosa Virulence-Related Genes Using a Caenorhabditis elegans Infection Model”揭示了美国哈佛医学院研究者的最新研究结果，在报告中，研究者用秀丽线虫感染模型，然后在全基因组的水平上揭示了和铜绿假单胞菌相关的毒性基因。

铜绿假单胞菌，又名绿脓杆菌，是一种革兰氏阴性机会致病菌，也是医院常见的获得性感染菌株，可以引发患者急慢性的感染，严重者可引发肺炎肺囊肿甚至肺癌。

<!--more-->

文章中，研究者用菌株PA14进行实验研究，他们用该菌株感染秀丽线虫（C.elegans），随后运用含有5850个单克隆的非冗余转座突变体文库来进行筛选在C.elegans感染过程中细菌所涉及到的毒力基因。使用的突变体文库可以覆盖绿脓杆菌将近80%的基因组范围。

通过实验，研究者们发现了180个不同的突变体菌株（转座子插入到了不同的毒力基因上），也就表明研究者发现了180个不同的毒力基因，这其中包括已知的和新型的毒力基因。7个以前其它功能的基因PchH、PchI、PepP、ClpA、PA0456、PA0745和PA14_27700发现均和细菌毒力相关。后期研究者检测了这些独立基因在细菌中的正常表达水平，并且构建了其系统分布图谱。

研究者揭示了，主要作用于C.elegans的毒性基因既不是绿脓杆菌基因组的特异性区域，也不是假设的转移基因组岛，或许是其它原核生物的共同的古老基因。 
<div id="ztload">
<div>
<div>

<img src="http://www.bioon.com/biology/UploadFiles/201208/2012080700145483.jpg" alt="" width="113" height="149" border="0" />

<a title="" href="http://dx.doi.org/doi:10.1371/journal.ppat.1002813" target="_blank">doi:10.1371/journal.ppat.1002813</a>
PMC:
PMID:

</div>
<div>

<br/><strong>Genome-Wide Identification of Pseudomonas aeruginosa Virulence-Related Genes Using a Caenorhabditis elegans Infection Model</strong><br/>


Rhonda L. Feinbaum1, Jonathan M. Urbach1, Nicole T. Liberati1, Slavica Djonovic1, Allison Adonizio1, Anne-Ruxandra Carvunis2, Frederick M. Ausubel1*

Pseudomonas aeruginosa strain PA14 is an opportunistic human pathogen capable of infecting a wide range of organisms including the nematode Caenorhabditis elegans. We used a non-redundant transposon mutant library consisting of 5,850 clones corresponding to 75% of the total and approximately 80% of the non-essential PA14 ORFs to carry out a genome-wide screen for attenuation of PA14 virulence in C. elegans. We defined a functionally diverse 180 mutant set (representing 170 unique genes) necessary for normal levels of virulence that included both known and novel virulence factors. Seven previously uncharacterized virulence genes (ABC transporters PchH and PchI, aminopeptidase PepP, ATPase/molecular chaperone ClpA, cold shock domain protein PA0456, putative enoyl-CoA hydratase/isomerase PA0745, and putative transcriptional regulator PA14_27700) were characterized with respect to pigment production and motility and all but one of these mutants exhibited pleiotropic defects in addition to their avirulent <a href="http://www.biodic.cn/search.asp?txtitle=phenotype" target="_blank">phenotype</a>. We examined the collection of genes required for normal levels of PA14 virulence with respect to occurrence in P. aeruginosa strain-specific genomic regions, location on putative and known genomic islands, and phylogenetic distribution across prokaryotes. Genes predominantly contributing to virulence in C. elegans showed neither a bias for strain-specific regions of the P. aeruginosa genome nor for putatively horizontally transferred genomic islands. Instead, within the collection of virulence-related PA14 genes, there was an overrepresentation of genes with a broad phylogenetic distribution that also occur with high frequency in many prokaryotic clades, suggesting that in aggregate the genes required for PA14 virulence in C. elegans are biased towards evolutionarily conserved genes.

<br/>来源：生物谷

</div>
</div>
</div>