Caspr1 is a Host Receptor for Meningitis-causing Escherichia Coli

Overview

Journal Nat Commun

Specialty Biology

Date 2018 Jun 14

PMID 29895952

Citations 26

Authors

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

De-Shu Shang

Bo Li

Qing-Chang Li

Liu Cao

Kwang Sik Kim

Yu-Hua Chen

Affiliations

Soon will be listed here.

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.

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