Escherichia coli hijack Caspr1 receptor to invade cerebral vascular and neuronal hosts.
Escherichia coli hijack Caspr1 receptor to invade cerebral vascular and neuronal hosts.
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大肠杆菌劫持Caspr1受体侵入脑血管和神经元宿主
DOI：
10.15698/mic2018.09.647
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发表时间：
2018-08-07
期刊：
影响因子：
--
通讯作者：
Chen YH
中科院分区：
文献类型：
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作者：
Zhao WD;Liu DX;Chen YH
大肠杆菌（E.大肠杆菌）穿透血脑屏障（BBB）是脑膜炎发展的关键步骤。在最近的一篇论文（Nat Commun 9：2296）中，我们鉴定Caspr 1为E.大肠杆菌毒力因子IbeA为细菌穿透血脑屏障铺平道路。细菌IbeA与内皮细胞Caspr 1相互作用，触发细胞内粘着斑激酶激活，导致E. coli内化到脑内皮细胞中。重要的是，内皮细胞敲除小鼠中Caspr 1显著降低了E.大肠杆菌穿过血脑屏障。基于Caspr 1胞外氨基酸203-355与IbeA结合的结果，我们测试了重组Caspr 1（203-355）肽在新生大鼠脑膜炎模型中的阻断作用。结果表明，Caspr 1（203-355）肽能有效地抑制大肠杆菌的生长。结果表明，Caspr 1（203-355）肽可用于中和强毒的IbeA，从而预防脑膜炎。我们进一步发现E.大肠杆菌可直接侵入海马神经元引起细胞凋亡，这需要细菌IbeA与神经元Caspr 1相互作用。这些结果表明，E.大肠杆菌劫持Caspr 1作为宿主受体，穿透血脑屏障并侵入海马神经元，导致脑膜炎的进展。
Escherichia coli (E. coli) penetration of the blood-brain barrier (BBB) is the key step essential for the development of meningitis. In a recent paper (Nat Commun 9:2296), we identify Caspr1 as a host receptor for E. coli virulence factor IbeA to pave the way the penetration of bacteria through the BBB. Bacterial IbeA interacts with endothelial Caspr1 to trigger intracellular focal adhesion kinase activation, leading to E. coli internalization into the brain endothelial cells. Importantly, endothelial knockout of Caspr1 in mice significantly reduced E. coli crossing through the BBB. Based on the results that extracellular aa 203-355 of Caspr1 bind with IbeA, we tested the blocking effect of recombinant Caspr1(203-355) peptides in neonatal rat model of meningitis. The results showed that Caspr1(203-355) peptides effectively attenuated E. coli penetration into the brain during meningitis, indicating that Caspr1(203-355) peptides could be used to neutralize the virulent IbeA to prevent meningitis. We further found that E. coli can directly invade into hippocampal neurons causing apoptosis which required the interaction between bacterial IbeA and neuronal Caspr1. These findings demonstrate that E. coli hijack Caspr1 as a host receptor for penetration of BBB and invasion of hippocampal neurons, resulting in progression of meningitis.