Study for the factor involved in endotoxin ercognition

鼠伤寒沙门氏菌重塑其外膜，包括脂多糖的脂质A组分，以在动物体内存活。通过宿主环境激活传感器激酶PhoQ，促进酶的合成，所述酶将氨基阿拉伯糖脱酰化、棕榈酰化、羟基化并连接至脂质A，其被称为内毒素。脱酰化和/或棕榈酰化脂质A物种的产生，我检查了他们的能力，诱导细胞信号通过Toll样受体4。沙门氏菌脂质A3-O-脱酰酶PagL是一种外膜蛋白，其表达受PhoQ调控。在PhoQ活化后，尽管诱导了PagL表达，但在鼠伤寒沙门氏菌中未检测到3-O-脱酰脂质A物质。与此相反，外膜氨基阿拉伯糖修饰缺陷的菌株表现出体内PagL活性，表明这种膜修饰抑制PagL酶活性。由于并非所有脂质A分子在PhoQ活化后都被氨基阿拉伯糖修饰，因此这些结果表明，PagL酶促脱酰作用被膜环境从其底物中螯合PagL或改变其构象所抑制。PagL依赖性脱酰检测在超声破坏膜和膜处理与octylglucoside，表明完整的膜的损害释放PagL的翻译后抑制。

Salmonella typhimurium remodels its outer membrane, including the lipid A component of lipopolysaccharide, to survive within animals. Activation of the sensor kinase PhoQ by host environments, promotes synthesis of enzymes that deacylate, palmitoylate, hydroxylate and attach aminoarabinose to lipid A, which is known as endotoxin. Deacylated- and/or palmitoylated-lipid A species were generated, and I examined their ability to induce cellular signaling through Toll-like receptor 4. The ability was reduced by the modifications, suggesting that the modifications are beneficial for bacteria to evade from host recognition.The Salmonellae lipid A 3-O-deacylase PagL, is an outer membrane protein whose expression is regulated by PhoQ. Upon PhoQ-activation, 3-O-deacylated lipid A species were not detected in S.typhimurium despite induction of the PagL expression. In contrast, strains defective for aminoarabinose modification of the outer membrane demonstrated in vivo PagL activity, indicating that this membrane modification inhibited PagL enzymatic activity. Since not all lipid A molecules are modified with aminoarabinose upon PhoQ-activation, these results suggested that PagL enzymatic deacylation was post-translationally inhibited by membrane environments sequestering PagL from its substrate or altering its conformations. PagL-dependent deacylation was detected in sonically disrupted membrane and membrane treated with octylglucoside, suggesting that damages of intact membrane releases PagL from the post-translational inhibition.