CONSTITUTIVE EXPRESSION OF THE PHOP REGULON ATTENUATES SALMONELLA VIRULENCE AND SURVIVAL WITHIN MACROPHAGES
CONSTITUTIVE EXPRESSION OF THE PHOP REGULON ATTENUATES SALMONELLA VIRULENCE AND SURVIVAL WITHIN MACROPHAGES
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DOI：
10.1128/jb.172.5.2485-2490.1990
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发表时间：
1990-05-01
影响因子：
3.2
通讯作者：
MEKALANOS, JJ
中科院分区：
文献类型：
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作者：
MILLER, SI;MEKALANOS, JJ
phoP 基因位点是一个由两部分组成的调节系统 (phoP-phoQ)，它控制鼠伤寒沙门氏菌毒力和巨噬细胞内生存所必需的基因表达。具有 phoP 组成型突变（表型 PhoPC）的菌株显示 phoP 激活基因（pag 位点）的表达比具有野生型 phoP 基因座（表型 PhoP+）的菌株高出 10 倍。虽然 phoP 组成型突变导致 pag 基因座的表达增加，但它也显着降低了其他蛋白质种类的表达。通过二维蛋白质凝胶电泳比较 PhoP+ 和 PhoPC 菌株的蛋白质含量表明，由于这种突变，至少 40 种不同的蛋白质种类的表达发生了变化。研究发现，PhoPC 鼠伤寒沙门氏菌的毒力和在巨噬细胞内的存活率均被减弱。这一发现表明，鼠伤寒沙门氏菌完全毒力需要平衡的 PhoP-PhoQ 调节反应，从而允许 phoP 抑制和激活基因的表达。我们进一步表明，少量的 PhoPC 细菌可以用作减毒活疫苗来预防小鼠伤寒。仅有少量的 PhoPC 细菌就能保护小鼠免受 105 50% 致死剂量的野生型生物体的攻击，这表明重要的保护性抗原受到 PhoP-PhoQ 毒力调节子的调节。
The phoP genetic locus is a two-component regulatory system (phoP-phoQ) that controls the expression of genes essential for Salmonella typhimurium virulence and survival within macrophages. Strains with a phoP constitutive mutation (phenotype PhoPC) showed up to 10-fold greater expression of phoP-activated genes (pag loci) than did strains with a wild-type phoP locus (phenotype PhoP+). While the phoP constitutive mutation resulted in increased expression of pag loci, it also dramatically reduced the expression of other protein species. Comparison of the protein content of PhoP+ and PhoPC strains by two-dimensional protein gel electrophoresis demonstrated that at least 40 separate protein species were changed in expression as a result of this mutation. The PhoPC S. typhimurium were found to be attenuated for virulence and survival within macrophages. This finding suggests that a balanced PhoP-PhoQ regulatory response, which allows expression of phoP-repressed as well as -activated genes, is required for full virulence of S. typhimurium. We have further shown that small numbers of PhoPC bacteria can be used as a live attenuated vaccine to protect against mouse typhoid. As few as PhoPC bacteria protected mice against challenge with 105 50% lethal doses of wild-type organisms, suggesting that important protective antigens are regulated by the PhoP-PhoQ virulence regulon.