Identification of PhoP-PhoQ activated genes within a duplicated region of the Salmonella typhimurium chromosome

Identification of PhoP-PhoQ activated genes within a duplicated region of the Salmonella typhimurium chromosome
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DOI:
10.1006/mpat.1998.0217
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发表时间:
1998-08-01
影响因子:
3.8
通讯作者:
Miller, SI
Miller, SI
中科院分区:
医学3区
文献类型:
--
作者:
Gunn, JS;Belden, WJ;Miller, SI

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沙门氏菌的毒力需要PhoP-PhoQ双组分调控系统。PhoP-PhoQ在被巨噬细胞吞噬后激活基因的转录,这是在吞噬体环境中生存所必需的。13个以前未定义的PhoP激活的基因融合MudJ和TnphoA(pagA,和E-P,分别)进行了克隆和测序。大多数pag产物与数据库中的蛋白质没有相似性,而其他产物被预测编码:UDP-葡萄糖脱氢酶(pagA);与E.大肠杆菌铝诱导基因(pagH);在与sinR基因相邻的沙门氏菌特有区域内编码的蛋白质(pagN);与耶尔森氏菌毒力质粒产物相似的蛋白质(pagO);和与大肠杆菌抗性所必需的CrcA相似的蛋白质。coli转化樟脑(pagP)。在所表征的pag中,只有pagK、M和O紧密连锁。pagJ和pagK被证明是不连锁的,但在DNA序列上几乎相同,因为每个都位于1.6 kb的DNA重复内。pagJ和pagK周围序列的翻译显示出与来自染色体外元件的蛋白质以及参与DNA转位和重排的蛋白质的相似性,这表明该区域可能是或已经是移动的元件。pagK,M和J的转录起始位点进行了测定,然而,与其他已知的pag基因启动子的比较未能揭示PhoP调节激活的共识序列。与鼠伤寒沙门氏菌pagK特异性探针杂交的DNA序列在S.这些基因在沙门氏菌血清型和肠杆菌科中不存在,表明这些基因对引起人类腹泻的广泛宿主范围沙门氏菌具有特异性。累积起来,这些数据进一步证明:(1)PhoP-PhoQ是产生不同包膜或分泌蛋白的全局调节剂;(2)PhoP-PhoQ调节冗余功能蛋白的产生;(3)pag通常位于其他肠杆菌科中不存在的水平获得DNA区域。(C)北京:科学出版社.
Salmonellae virulence requires the PhoP-PhoQ two-component regulatory system. PhoP-PhoQ activate the transcription of genes following phagocytosis by macrophages which are necessary for survival within the phagosome environment. Thirteen previously undefined PhoP-activated gene fusions generated by MudJ and TnphoA (pag A, and E-P, respectively) were cloned and sequenced. Mostpag products show no similarity to proteins in the database, while others are predicted to encode: a UDP-glucose dehydrogenase (pagA); a protein with similarity to the product of an E. coli aluminium-induced gene (pagH); a protein encoded within a Salmonella-unique region adjacent to the sinR gene (pagN); a protein similar to a product of the Yersinia virulence plasmid (pagO); and a protein with similarity to CrcA which is necessary for resistance of E. coli to camphor (pagP). Of the pag characterized, only pagK, M and O were closely linked. pagJ and pagK were shown to be unlinked but nearly identical in DNA sequence, as each was located within a 1.6 kb DNA duplication. The translations of sequences surrounding pagJ and pagK show similarity to proteins from extrachromosomal elements as well as those involved in DNA transposition and rearrangement, suggesting that this region may have been or is a mobile element. The transcriptional start sites of pagK, M, and J were determined; however, comparison to other known pag gene promoters failed to reveal a consensus sequence for PhoP-regulated activation. DNA sequences hybridizing to a Salmonella typhimurium pagK specific probe were found in S. enteritidis but absent in other Salmonella serotypes and Enterobacteriaceae tested, suggesting that these genes are specific for broad host range Salmonellae that cause diarrhoea in humans. Cumulatively, these data further demonstrate: (1) that PhoP-PhoQ is a global regulator of the production of diverse envelope or secreted proteins; (2) that PhoP-PhoQ regulate the production of proteins of redundant function; and (3) that pag are often located in regions of horizontally acquired DNA that are absent in other Enterobacteriaceae. (C) 1998 Academic Press.