Salmonella enterica serovar Typhimurium periplasmic superoxide dismutase SodCI is a member of the PhoPQ regulon and is induced in macrophages
Salmonella enterica serovar Typhimurium periplasmic superoxide dismutase SodCI is a member of the PhoPQ regulon and is induced in macrophages
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DOI：
10.1128/jb.00706-06
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发表时间：
2006-11-01
影响因子：
3.2
通讯作者：
Slauch, James M.
中科院分区：
文献类型：
--
作者：
Golubeva, Yekaterina A.;Slauch, James M.
鼠伤寒沙门氏菌在全身感染阶段在宿主巨噬细胞内复制。在巨噬细胞中，细菌必须在产生超氧化物的呼吸爆发中存活。鼠伤寒血清型菌株14028产生两种周质超氧化物歧化酶SodCI和SodCII，但只有SodCI有助于毒力。虽然我们已经证明这主要是由于两种蛋白质的差异，但有证据表明这两种基因的差异调节。使用转录sodCI-和sodCII-lac融合，我们表明，sodCII的RpoS西格玛因子的控制下，是已知的大肠杆菌直系同源物，sodC。相比之下，我们表明，sodCI是转录控制的PhoPQ双组分调控系统，调节巨噬细胞生存所需的毒力基因阵列。将phoP无效突变引入sodCI融合菌株导致转录降低和调控丧失。sodCI-lac融合体在含有phoQ组成型等位基因的背景中显示高水平表达。sodCI基因在从受感染小鼠的组织培养巨噬细胞或脾脏回收的细菌中诱导15倍。巨噬细胞中的诱导依赖于PhoP。在巨噬细胞和动物中，sodCII融合被诱导三到四倍;这种诱导不受PhoP损失的影响。因此，由Giffsy-2噬菌体水平转移的sodCl受PhoPQ调节，使得其在适当的时间和地点被诱导以对抗吞噬性超氧化物。
Salmonella enterica serovar Typhimurium replicates within host macrophages during the systemic stage of infection. In the macrophage, the bacteria must survive the respiratory burst that produces superoxide. Serovar Typhimurium strain 14028 produces two periplasmic superoxide dismutases, SodCI and SodCII, but only SodCI contributes to virulence. Although we have shown that this is primarily due to differences in the two proteins, evidence suggests differential regulation of the two genes. Using transcriptional sodCI- and sodCII-lac fusions, we show that sodCII is under the control of the RpoS sigma factor, as was known for the Escherichia coli ortholog, sodC. In contrast, we show that sodCI is transcriptionally controlled by the PhoPQ two-component regulatory system, which regulates an array of virulence genes required for macrophage survival. Introduction of a phoP-null mutation into the sodCI fusion strain resulted in a decrease in transcription and loss of regulation. The sodCI-lac fusion showed high-level expression in a background containing a phoQ constitutive allele. The sodCI gene is induced 15-fold in bacteria recovered from either the tissue culture macrophages or the spleens of infected mice. Induction in macrophages is dependent on PhoP. The sodCII fusion was induced three- to fourfold in macrophages and animals; this induction was unaffected by loss of PhoP. Thus, sodCI, which is horizontally transferred by the Gifsy-2 phage, is regulated by PhoPQ such that it is induced at the appropriate time and place to combat phagocytic superoxide.