A small protein that mediates the activation of a two-component system by another two-component system

A small protein that mediates the activation of a two-component system by another two-component system
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DOI:
10.1093/emboj/19.8.1861
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发表时间:
2000-04-17
期刊:
影响因子:
11.4
通讯作者:
Groisman, EA
Groisman, EA
中科院分区:
生物学1区
文献类型:
--
作者:
Kox, LFF;Wösten, MMSM;Groisman, EA

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肠沙门氏菌的 PmrA-PmrB 双组分系统控制着对肽抗生素多粘菌素 B 和来自人中性粒细胞的几种抗菌蛋白的耐药性。 PmrA 激活基因的转录是由高铁诱导的,但也可以通过低镁生长来促进,这一过程需要另一个双组分系统 PhoP-PhoQ。在这里,我们定义了 PhoP-PhoQ 和 PmrA-PmrB 系统之间相互作用的遗传基础。我们已经确定 pmrD 是一种 PhoP 激活基因,在低镁生长过程中介导 PmrA 调节基因的转录激活。当 pmrD 的转录由异源启动子驱动时,PmrA 激活基因的表达甚至在抑制镁浓度下也会发生,并且变得独立于 phoP 和 phoQ 基因。 PmrD 效应对 PmrA 调节基因具有特异性,并且需要功能性 PmrA 和 PmrB 蛋白。如果在低镁条件下生长,pmrD 突变体对多粘菌素敏感,但如果在高铁条件下生长则对多粘菌素敏感。 PmrD 蛋白在转录后水平控制 PmrA-PmrB 系统的活性。
The PmrA-PmrB two-component system of Salmonella enterica controls resistance to the peptide antibiotic polymyxin B and to several antimicrobial proteins from human neutrophils. Transcription of PmrA-activated genes is induced by high iron, but can also be promoted by growth in low magnesium in a process that requires another two-component system, PhoP-PhoQ. Here, we define the genetic basis for the interaction between the PhoP-PhoQ and PmrA-PmrB systems. We have identified pmrD as a PhoP-activated gene that mediates the transcriptional activation of PmrA-regulated genes during growth in low magnesium. When transcription of pmrD is driven from a heterologous promoter, expression of PmrA-activated genes occurs even at repressing magnesium concentrations and becomes independent of the phoP and phoQ genes. The PmrD effect is specific for PmrA-regulated genes and requires functional PmrA and PmrB proteins, A pmrD mutant is sensitive to polymyxin if grown in low magnesium, but resistant if grown in high iron. The PmrD protein controls the activity of the PmrA-PmrB system at a post-transcriptional level.