Regulation of lipid a modifications by Salmonella typhimurium virulence genes phoP-phoQ
Regulation of lipid a modifications by Salmonella typhimurium virulence genes phoP-phoQ
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DOI：
10.1126/science.276.5310.250
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发表时间：
1997-04-11
期刊：
影响因子：
56.9
通讯作者：
Miller, SI
中科院分区：
文献类型：
--
作者：
Guo, L;Lim, KB;Miller, SI
细菌的致病机制需要能够感知宿主微环境并通过调节毒力基因转录来应答的蛋白质。对于鲑鱼，一种这样的调节系统是PhoP-PhoQ，其调节细胞内存活和对阳离子肽的抗性所需的基因。质谱分析显示，鼠伤寒沙门氏菌PhoP-PhoQ调节脂质A的结构修饰，脂多糖（LPS）的宿主信号传导部分，通过添加氨基阿拉伯糖和2-羟基肉豆蔻酸。结构修饰的脂质A改变了LPS介导的内皮细胞粘附分子E-选择素表达和粘附单核细胞肿瘤坏死因子-α表达。因此，对环境诱导的脂质A结构修饰的反应改变可能代表细菌在宿主组织内获得优势的机制。
Bacterial pathogenesis requires proteins that sense host microenvironments and respond by regulating virulence gene transcription. For Salmonellae, one such regulatory system is PhoP-PhoQ, which regulates genes required for intracellular survival and resistance to cationic peptides. Analysis by mass spectrometry revealed that Salmonella typhimurium PhoP-PhoQ regulated structural modifications of lipid A, the host signaling portion of lipopolysaccharide (LPS), by the addition of aminoarabinose and 2-hydroxymyristate. Structurally modified lipid A altered LPS-mediated expression of the adhesion molecule E-selectin by endothelial cells and tumor necrosis factor-alpha expression by adherent monocytes. Thus, altered responses to environmentally induced lipid A structural modifications may represent a mechanism for bacteria to gain advantage within host tissues.