A 2-COMPONENT REGULATORY SYSTEM (PHOP-PHOQ) CONTROLS SALMONELLA-TYPHIMURIUM VIRULENCE
A 2-COMPONENT REGULATORY SYSTEM (PHOP-PHOQ) CONTROLS SALMONELLA-TYPHIMURIUM VIRULENCE
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DOI：
10.1073/pnas.86.13.5054
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发表时间：
1989-07-01
影响因子：
11.1
通讯作者：
MEKALANOS, JJ
中科院分区：
文献类型：
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作者：
MILLER, SI;KUKRAL, AM;MEKALANOS, JJ
我们已经确定，鼠伤寒沙门氏菌菌株与突变的正调控位点phoP显着减弱对BALB/c小鼠的毒力。phoP基因座的DNA序列表明，它是由两个基因存在于一个操纵子，称为phoP和phoQ。推导的phoP和phoQ基因产物的氨基酸序列与响应环境刺激的细菌双组分转录调节因子的其他成员高度相似。S.已经分离出具有转座子插入的鼠伤寒菌株，它们产生需要phoP和phoQ表达的转录和翻译基因融合，并且具有不同的染色体位置，表明该系统是调节子。其中一个融合菌株含有一个称为pagC的基因突变，具有毒力缺陷。其他菌株，包括在编码酸性磷酸酶的phoN基因中含有突变的菌株，具有野生型毒力。具有pagC、phoP或phoQ突变的菌株在培养的小鼠巨噬细胞中的存活率降低。当在小鼠中用作活疫苗时，具有phoP或phoQ突变的菌株对随后的野生型S.鼠伤寒。
We have determine that Salmonella typhimurium strains with mutations in the positive regulatory locus phoP are markedly attenuated in virulence for BALB/c mice. The DNA sequence for the phoP locus indicates that it is composed of two genes presented in an operon, termed phoP and phoQ. The deduced amino acid sequences of the phoP and phoQ gene products are highly similar to other members of bacterial two-component transcriptional regulators that respond to environmental stimuli. S. typhimurium strains with transposon insertions that create transcriptional and translational gene fusions that require phoP and phoQ for expression havebeen isolated and have different chromosomal locations, indicating that this system is a regulon. One of these fusion strains, containing a mutation in a gene termed pagC, has a virulence defect. Other strains, including those containing mutations in the phoN gene, encoding an acid phosphatase, have wild-type virulence. Strains with pagC, phoP, or phoQ mutations have decreased survival in cultured mouse macrophages. When used as live vaccines in mice, strains with phoP or phoQ mutations afford partial protection to subsequent challenge by wild-type S. typhimurium.