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, De Shu Shang, Bo Li, Qing Chang Li, Liu Cao, Kwang Sik Kim, Yu Hua Chen

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number2296
JournalNature Communications
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2018

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ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Zhao, W. D., Liu, D. X., Wei, J. Y., Miao, Z. W., Zhang, K., Su, Z. K., Zhang, X. W., Li, Q., Fang, W. G., Qin, X. X., Shang, D. S., Li, B., Li, Q. C., Cao, L., Kim, K. S., & Chen, Y. H. (2018). Caspr1 is a host receptor for meningitis-causing Escherichia coli. Nature Communications, 9(1), [2296]. https://doi.org/10.1038/s41467-018-04637-3