Salmonella AvrA effector inhibits the key proinflammatory, anti-apoptotic NF-κB pathway
Salmonella AvrA effector inhibits the key proinflammatory, anti-apoptotic NF-κB pathway
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DOI：
10.4049/jimmunol.169.6.2846
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发表时间：
2002-09-15
影响因子：
4.4
通讯作者：
Neish, AS
中科院分区：
文献类型：
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作者：
Collier-Hyams, LS;Zeng, H;Neish, AS
分泌的原核效应蛋白已经进化为调节特定真核宿主的细胞功能。通常，这些蛋白质被认为是促进寄生的毒力因子。然而，在某些植物和昆虫的真核/原核关系中，效应蛋白参与了共生或共生相互作用的建立。在这项研究中，我们报告说，从鼠伤寒沙门氏菌，人类常见的肠道病原体的AvrA蛋白，是一种效应分子，抑制激活的关键促炎性NF-κ B转录因子，并增加人类上皮细胞的凋亡。该活性与针对YopJ（由细菌病原体耶尔森氏菌表达的AvrA同源物）所描述的活性相似但在机制上不同。我们认为，AvrA可能会限制在脊椎动物中的毒力在植物中的无毒因子类似的方式，因此，是第一个细菌效应从哺乳动物病原体已被赋予这样的功能。
Secreted prokaryotic effector proteins have evolved to modulate the cellular functions of specific eukaryotic hosts. Generally, these proteins are considered virulence factors that facilitate parasitism. However, in certain plant and insect eukaryotic/prokaryotic relationships, effector proteins are involved in the establishment of commensal or symbiotic interactions. In this study, we report that the AvrA protein from Salmonella typhimurium, a common enteropathogen of humans, is an effector molecule that inhibits activation of the key proinflammatory NF-kappaB transcription factor and augments apoptosis in human epithelial cells. This activity is similar but mechanistically distinct from that described for YopJ, an AvrA homolog expressed by the bacterial pathogen Yersinia. We suggest that AvrA may limit virulence in vertebrates in a manner analogous to avirulence factors in plants, and as such, is the first bacterial effector from a mammalian pathogen that has been ascribed such a function.