Type III secretion chaperone-dependent regulation:: activation of virulence genes by SicA and InvF in Salmonella typhimurium
Type III secretion chaperone-dependent regulation:: activation of virulence genes by SicA and InvF in Salmonella typhimurium
复制标题
DOI：
10.1093/emboj/20.8.1850
复制
发表时间：
2001-04-17
期刊：
影响因子：
11.4
通讯作者：
Miller, VL
中科院分区：
文献类型：
--
作者：
Darwin, KH;Miller, VL
沙门氏菌对肠上皮的入侵需要在许多细菌病原体中常见的III型分泌系统（TTSS）。TTSS将效应蛋白从细菌转运到真核细胞中。这些效应子操纵细胞功能以有益于病原体。在人类和动物病原体鼠伤寒沙门氏菌中，编码分泌的效应子分子Sip/Ssp ABCD、SigD、SptP和SopE的基因的表达需要AraC/XylS样调节子InvF和分泌伴侣SicA两者。在这项工作中，在三个操纵子的启动子区域中鉴定了InvF结合位点，SicA似乎不影响InvF稳定性，也不直接结合DNA。然而，SicA可以与InvF共纯化，表明InvF和SicA相互作用以激活效应基因启动子的转录。这是蛋白辅因子和AraC/XylS家族转录调节因子之间的接触的第一个证明，此外，是转录调节因子和TTSS伴侣之间相互作用的第一个直接证据。这里描述的InvF和SicA的效应基因的调节可能代表了在各种病原体中调节毒力的新范例。
Invasion of the intestinal epithelium by Salmonella sp, requires a type III secretion system (TTSS) common in many bacterial pathogens. TTSS translocate effector proteins from bacteria into eukaryotic cells. These effecters manipulate cellular functions in order to benefit the pathogen, In the human and animal pathogen Salmonella typhimurium, the expression of genes encoding the secreted effector molecules Sip/Ssp ABCD, SigD, SptP and SopE requires both the AraC/XylS-like regulator InvF and the secretion chaperone SicA, In this work, an InvF binding site was identified in the promoter regions of three operons, SicA does not appear to affect InvF stability nor to bind DNA directly. However, SicA could be co-purified with InvF, suggesting that InvF and SicA interact with each other to activate transcription from the effector gene promoters. This is the first demonstration of a contact between a protein cofactor and an AraC/XylS family transcriptional regulator and, moreover, is the first direct evidence of an interaction between a transcriptional regulator and a TTSS chaperone. The regulation of effector genes described here for InvF and SicA may represent a new paradigm for regulation of virulence in a wide variety of pathogens.