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成分，以在动物体内生存。宿主环境激活感应激酶PhoQ，促进脱酰基化、棕榈酰化、羟化和将阿拉伯氨基糖附着在脂质A上的酶的合成，这被称为内毒素。生成去酰化和/或棕榈酰化脂质A种，并检测了它们通过toll样受体4诱导细胞信号传导的能力。这些修饰降低了这种能力，表明这些修饰有利于细菌逃避宿主的识别。沙门氏菌脂质A 3- o -去乙酰化酶PagL是一种外膜蛋白，其表达受PhoQ调控。phoq激活后，鼠伤寒沙门氏菌虽然诱导了PagL的表达，但没有检测到3- o -去乙酰化脂质A。相比之下，外膜氨基阿拉伯糖修饰缺陷的菌株在体内表现出PagL活性，表明这种膜修饰抑制了PagL酶的活性。由于phoq激活后并非所有的脂质A分子都被阿拉伯糖氨基糖修饰，这些结果表明，PagL酶的去乙酰化在翻译后被膜环境所抑制，膜环境将PagL从底物中隔离或改变其构象。在超声破坏膜和辛基葡萄糖苷处理的膜中检测到PagL依赖的去酰化，这表明完整膜的损伤使PagL从翻译后抑制中释放出来。

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.