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Further characterization of the PhoP regulon: identification of new PhoP-activated virulence loci.

机译:PhoP调节子的进一步表征:鉴定新的PhoP激活的毒力基因座。

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Salmonella typhimurium survival within macrophages is an essential virulence property necessary to enteric fever pathogenesis. This survival requires coordinate transcriptional activation of virulence genes within acidified macrophage phagosomes. Virulence gene transcription is regulated by a two-component system comprising the PhoP (transcriptional activator) and PhoQ (sensor-kinase) proteins. Thirteen new PhoP-activated loci (designated pagD to pagP) encoding membrane or secreted proteins have been identified by use of the transposon TnphoA. Three of these loci have a chromosomal location that was linked to the previously identified pagC locus. Strains with TnphoA insertions in pagD, pagJ, pagK, and pagM were significantly attenuated for mouse virulence (50% lethal dose greater than 1,000 times that of wild-type bacteria). No strains with pag::TnphoA insertions were found to have altered sensitivity to the cationic antimicrobial peptide NP-1 defensin. PhoP and PhoQ are pleotropic regulators of membrane or secreted proteins, suggesting that the ability to effect a global change in the expression of these proteins is required for S. typhimurium survival within acidified macrophage phagosomes.
机译:鼠伤寒沙门氏菌在巨噬细胞中的存活是肠热发病机理所必需的必不可少的毒力特性。这种生存需要酸化巨噬细胞吞噬体内毒力基因的协调转录激活。毒力基因转录受包含PhoP(转录激活因子)和PhoQ(传感器激酶)蛋白的两组分系统调控。通过使用转座子TnphoA,已鉴定出十三个新的PhoP激活基因座(称为pagD至pagP)编码膜或分泌蛋白。这些基因座中的三个具有与先前鉴定的pagC基因座相关的染色体位置。 pagD,pagJ,pagK和pagM中插入TnphoA的菌株对小鼠的毒力显着减弱(50%的致死剂量大于野生型细菌的1000倍)。没有发现插入pag :: TnphoA的菌株对阳离子抗菌肽NP-1防御素的敏感性发生了改变。 PhoP和PhoQ是膜或分泌蛋白的多效性调节剂,表明在酸性巨噬细胞吞噬体中鼠伤寒沙门氏菌的存活需要影响这些蛋白表达的整体变化的能力。

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