Division of Biological Sciences, University of California, San Diego, CA 92093, USA.
Proc Natl Acad Sci U S A. 2010 Feb 2;107(5):2153-8. doi: 10.1073/pnas.0914643107. Epub 2010 Jan 21.
Very little is known about how animals discriminate pathogens from innocuous microbes. To address this question, we examined infection-response gene induction in the nematode Caenorhabditis elegans. We focused on genes that are induced in C. elegans by infection with the bacterial pathogen Pseudomonas aeruginosa, but are not induced by an isogenic attenuated gacA mutant. Most of these genes are induced independently of known immunity pathways. We generated a GFP reporter for one of these genes, infection response gene 1 (irg-1), which is induced strongly by wild-type P. aeruginosa strain PA14, but not by other C. elegans pathogens or by other wild-type P. aeruginosa strains that are weakly pathogenic to C. elegans. To identify components of the pathway that induces irg-1 in response to infection, we performed an RNA interference screen of C. elegans transcription factors. This screen identified zip-2, a bZIP transcription factor that is required for inducing irg-1, as well as several other genes, and is important for defense against infection by P. aeruginosa. These data indicate that zip-2 is part of a specialized pathogen response pathway that is induced by virulent strains of P. aeruginosa and provides defense against this pathogen.
人们对于动物如何区分病原体和无害微生物知之甚少。为了解决这个问题，我们研究了线虫秀丽隐杆线虫感染反应基因的诱导。我们专注于那些能被细菌病原体铜绿假单胞菌感染诱导，但不能被同源减毒 gacA 突变体诱导的基因。这些基因中的大多数都不依赖于已知的免疫途径而被诱导。我们生成了一个这些基因中的一个的 GFP 报告基因，感染应答基因 1（irg-1），它能被野生型铜绿假单胞菌菌株 PA14 强烈诱导，但不能被其他线虫病原体或对线虫致病性较弱的其他野生型铜绿假单胞菌菌株诱导。为了鉴定诱导irg-1的通路组分，我们对线虫转录因子进行了 RNA 干扰筛选。该筛选鉴定出了 zip-2，它是一种 bZIP 转录因子，对于诱导 irg-1 以及其他几个基因是必需的，并且对于抵抗铜绿假单胞菌的感染很重要。这些数据表明，zip-2 是一个由毒力株铜绿假单胞菌诱导的专门病原体反应途径的一部分，为该病原体提供了防御。
