Lpp of Escherichia coli K1 inhibits host ROS production to counteract neutrophil-mediated elimination.
Lpp of Escherichia coli K1 inhibits host ROS production to counteract neutrophil-mediated elimination.
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大肠杆菌 K1 的 Lpp 抑制宿主 ROS 产生，以抵消中性粒细胞介导的消除
DOI：
10.1016/j.redox.2022.102588
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发表时间：
2023-02
期刊：
影响因子：
11.4
通讯作者：
Zhao, Wei-Dong
中科院分区：
文献类型：
--
作者：
Zhang, Xue-Wei;An, Ming-Xin;Huang, Zeng-Kang;Ma, Lan;Zhao, Dan;Yang, Zhao;Shi, Jun-Xiu;Liu, Dong-Xin;Li, Qiang;Wu, An-Hua;Chen, Yu-Hua;Zhao, Wei-Dong
大肠杆菌（E.大肠杆菌）是引起新生儿脑膜炎的最常见的革兰氏阴性细菌。对E.大肠杆菌脑膜炎，特别是如何E.大肠杆菌能否逃脱宿主的免疫防御，仍有待澄清。在这里，我们表明，删除细菌Lpp编码脂蛋白显着降低致病性的E。coliK1诱导脑膜炎所必需的高度菌血症。Lpp缺失的E. coli K1对中性粒细胞的胞内杀菌活性敏感，而不影响中性粒细胞胞外陷阱的释放。代表中性粒细胞中主要抗菌机制的活性氧（ROS）的产生在对Lpp缺失的E.杆菌我们发现这种增强的ROS反应与中性粒细胞中NADPH氧化酶p47phox和p67phox的膜转位有关。构建p47phox基因敲除小鼠，观察Lpp缺失的E. p47phox基因敲除后，大肠杆菌中p47phox基因的表达显著恢复。蛋白质组学分析表明，Lpp缺陷诱导鞭毛蛋白FliC在E.杆菌我们进一步证明了FliC是Lpp缺失的E.杆菌总之，这些数据揭示了Lpp在促进E.大肠杆菌K1。由此推断，E.大肠杆菌K1能够抑制FliC表达，从而抑制中性粒细胞中NADPH氧化酶的激活，导致杀菌活性减弱，从而保护大肠杆菌。大肠杆菌K1的中性粒细胞消除。Lpp基因在E.大肠杆菌显著抑制其诱导脑膜炎的高度菌血症的能力。嗜中性粒细胞对Lpp缺失的E.杆菌Lpp缺失E.大肠杆菌诱导中性粒细胞中NADPH氧化酶p67phox和p47phox的上调和膜移位。Lpp缺失的E.在p47phox敲除小鼠中恢复了诱导脑膜炎菌血症的大肠杆菌。Lpp缺陷上调鞭毛蛋白FliC在大肠杆菌中的表达。大肠杆菌，其在中性粒细胞中触发更强的ROS。
Escherichia coli (E. coli) is the most common Gram-negative bacterial organism causing neonatal meningitis. The pathogenesis of E. coli meningitis, especially how E. coli escape the host immune defenses, remains to be clarified. Here we show that deletion of bacterial Lpp encoding lipoprotein significantly reduces the pathogenicity of E. coli K1 to induce high-degree of bacteremia necessary for meningitis. The Lpp-deleted E. coli K1 is found to be susceptible to the intracellular bactericidal activity of neutrophils, without affecting the release of neutrophil extracellular traps. The production of reactive oxygen species (ROS), representing the primary antimicrobial mechanism in neutrophils, is significantly increased in response to Lpp-deleted E. coli. We find this enhanced ROS response is associated with the membrane translocation of NADPH oxidase p47phox and p67phox in neutrophils. Then we constructed p47phox knockout mice and we found the incidence of bacteremia and meningitis in neonatal mice induced by Lpp-deleted E. coli is significantly recovered by p47phox knockout. Proteomic profile analysis show that Lpp deficiency induces upregulation of flagellar protein FliC in E. coli. We further demonstrate that FliC is required for the ROS induction in neutrophils by Lpp-deleted E. coli. Taken together, these data uncover the novel role of Lpp in facilitating intracellular survival of E. coli K1 within neutrophils. It can be inferred that Lpp of E. coli K1 is able to suppress FliC expression to restrain the activation of NADPH oxidase in neutrophils resulting in diminished bactericidal activity, thus protecting E. coli K1 from the elimination by neutrophils. Deletion of Lpp gene in E. coli significantly inhibits its ability to induce high-degree of bacteremia for meningitis. The production of ROS in neutrophils is significantly increased in response to Lpp-deleted E. coli. Lpp-deleted E. coli induces upregulation and membrane translocation of the NADPH oxidase p67phox and p47phox in neutrophils. The ability of Lpp-deleted E. coli to induce bacteremia for meningitis is recovered in the p47phox knockout mice. Lpp deficiency upregulates the expression of flagellar protein FliC in E. coli which triggers stronger ROS in neutrophils.
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影响因子：
5.6
作者：
Nedeljković M;Sastre DE;Sundberg EJ
通讯作者：
Sundberg EJ
影响因子：
3.6
作者：
El-Naggar, Walid;Afifi, Jehier;Shah, Prakesh S.
通讯作者：
Shah, Prakesh S.
影响因子：
4.4
作者：
Crawford, Matthew A.;Aylott, Caroline V.;Bokoch, Gary M.
通讯作者：
Bokoch, Gary M.
影响因子：
20.3
作者：
Chen, Kan;Nishi, Hiroshi;Mayadas, Tanya N.
通讯作者：
Mayadas, Tanya N.
影响因子：
3.4
作者：
Maruvada R;Argon Y;Prasadarao NV
通讯作者：
Prasadarao NV