Caspr1 is a host receptor for meningitis-causing Escherichia coli

Wei-Dong Zhao (), Dong-Xin Liu, Jia-Yi Wei, Zi-Wei Miao, Ke Zhang, Zheng-Kang Su, Xue-Wei Zhang, Qiang Li, Wen-Gang Fang, Xiao-Xue Qin, Shang De-Shu, Bo Li, Qing-Chang Li, Liu Cao, Kwang Sik Kim and Yu-Hua Chen ()
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Wei-Dong Zhao: China Medical University
Dong-Xin Liu: China Medical University
Jia-Yi Wei: China Medical University
Zi-Wei Miao: China Medical University
Ke Zhang: China Medical University
Zheng-Kang Su: China Medical University
Xue-Wei Zhang: China Medical University
Qiang Li: China Medical University
Wen-Gang Fang: China Medical University
Xiao-Xue Qin: China Medical University
Shang De-Shu: China Medical University
Bo Li: China Medical University
Qing-Chang Li: China Medical University
Liu Cao: China Medical University
Kwang Sik Kim: Johns Hopkins University School of Medicine
Yu-Hua Chen: China Medical University

Nature Communications, 2018, vol. 9, issue 1, 1-16

Abstract: Abstract Escherichia coli is the leading cause of neonatal Gram-negative bacterial meningitis, but the pathogenesis of E. coli meningitis remains elusive. E. coli penetration of the blood–brain barrier (BBB) is the critical step for development of meningitis. Here, we identify Caspr1, a single-pass transmembrane protein, as a host receptor for E. coli virulence factor IbeA to facilitate BBB penetration. Genetic ablation of endothelial Caspr1 and blocking IbeA–Caspr1 interaction effectively prevent E. coli penetration into the brain during meningitis in rodents. IbeA interacts with extracellular domain of Caspr1 to activate focal adhesion kinase signaling causing E. coli internalization into the brain endothelial cells of BBB. E. coli can invade hippocampal neurons causing apoptosis dependent on IbeA–Caspr1 interaction. Our results indicate that E. coli exploits Caspr1 as a host receptor for penetration of BBB resulting in meningitis, and that Caspr1 might be a useful target for prevention or therapy of E. coli meningitis.

Date: 2018
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DOI: 10.1038/s41467-018-04637-3

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