Therapeutic development of group B Streptococcus meningitis by targeting a host cell signaling network involving EGFR.
Therapeutic development of group B Streptococcus meningitis by targeting a host cell signaling network involving EGFR.
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DOI：
10.15252/emmm.202012651
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发表时间：
2021-03-05
影响因子：
11.1
通讯作者：
Sik Kim K
中科院分区：
文献类型：
--
作者：
Zhu N;Zhang C;Prakash A;Hou Z;Liu W;She W;Morris A;Sik Kim K
B族链球菌（GBS）仍然是引起新生儿脑膜炎的最常见的革兰氏阳性菌，GBS脑膜炎仍然是死亡和发病的重要原因。在这项研究中，我们发现GBS渗透到大脑中最初发生在脑膜和皮质毛细血管中，并利用由S1P2，EGFR和CysLT 1组成的定义的宿主细胞信号网络。通过使用药理学抑制、基因敲除和敲低细胞、基因敲除动物靶向S1P2、EGFR和CysLT 1以及网络询问（彼此的上游和下游），证明了GBS在血脑屏障渗透中利用这种网络。更重要的是，抵消这些目标作为抗生素治疗的辅助治疗是有益的，在改善GBS脑膜炎动物的结果。这些研究结果表明，调查GBS的血脑屏障渗透提供了一种新的方法治疗GBS脑膜炎的发展。B族链球菌（GBS）利用特异性宿主因子S1 P2、EGFR和CysLT 1穿透血脑屏障，这是GBS脑膜炎发展的关键步骤。这些宿主因子作为一个独特的网络发挥作用，S1P2和CysLT 1作为EGFR的上游和下游分子。
Group B Streptococcus (GBS) remains the most common Gram‐positive bacterium causing neonatal meningitis and GBS meningitis continues to be an important cause of mortality and morbidity. In this study, we showed that GBS penetration into the brain occurred initially in the meningeal and cortex capillaries, and exploits a defined host cell signaling network comprised of S1P2, EGFR, and CysLT1. GBS exploitation of such network in penetration of the blood–brain barrier was demonstrated by targeting S1P2, EGFR, and CysLT1 using pharmacological inhibition, gene knockout and knockdown cells, and gene knockout animals, as well as interrogation of the network (up‐ and downstream of each other). More importantly, counteracting such targets as a therapeutic adjunct to antibiotic therapy was beneficial in improving the outcome of animals with GBS meningitis. These findings indicate that investigating GBS penetration of the blood–brain barrier provides a novel approach for therapeutic development of GBS meningitis. Group B Streptococci (GBS) exploit specific host factors S1P2, EGFR and CysLT1 to penetrate the blood‐brain barrier, which is the essential step in the development of GBS meningitis. These host factors function as a distinct network, with S1P2 and CysLT1 acting as upstream and downstream molecules of EGFR.
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DOI：
10.1038/nrmicro1952
发表时间：
2008-08
期刊：
Nature reviews. Microbiology
影响因子：
--
作者：
通讯作者：
--
DOI：
10.1158/1078-0432.ccr-16-2363
发表时间：
2017-08-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Britten CD;Garrett-Mayer E;Chin SH;Shirai K;Ogretmen B;Bentz TA;Brisendine A;Anderton K;Cusack SL;Maines LW;Zhuang Y;Smith CD;Thomas MB
通讯作者：
Thomas MB
不同浓度和温度下丁香酚对不同规格草虾的麻醉效果
影响因子：
4.6
作者：
Li Y;She Q;Han Z;Sun N;Liu X;Li X
通讯作者：
Li X
影响因子：
5.5
作者：
Kim, YV;Di Cello, F;Kim, KS
通讯作者：
Kim, KS
影响因子：
4.6
作者：
Duah, Ernest;Adapala, Ravi K.;Al-Azzam, Nosayba;Kondeti, Vinay;Gombedza, Farai;Thodeti, Charles K.;Paruchuri, Sailaja
通讯作者：
Paruchuri, Sailaja