Nature communications, 2018-06, Vol.9 (1), p.2296-16, Article 2296
2018
Details
- Autor(en) / Beteiligte
- Titel
- Caspr1 is a host receptor for meningitis-causing Escherichia coli
- Ist Teil von
- Nature communications, 2018-06, Vol.9 (1), p.2296-16, Article 2296
- Ort / Verlag
- England: Nature Publishing Group
- Erscheinungsjahr
- 2018
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2041-1723eISSN: 2041-1723DOI: 10.1038/s41467-018-04637-3Titel-ID: cdi_doaj_primary_oai_doaj_org_article_2284a8655d2b415395c6982bdf49525d
- Format
- –
- Schlagworte
- Animals, Apoptosis, Bacteria, Blood-Brain Barrier, Brain, Brain - metabolism, Cell Adhesion Molecules, Neuronal - metabolism, Cell Membrane - metabolism, Cell Survival, E coli, Endothelial cells, Endothelial Cells - metabolism, Escherichia coli, Escherichia coli - pathogenicity, Escherichia coli Proteins - metabolism, Female, Focal adhesion kinase, Focal Adhesion Kinase 1 - metabolism, HEK293 Cells, Hippocampus, Hippocampus - metabolism, Humans, Internalization, Kinases, Male, Membrane Proteins - metabolism, Meningitis, Meningitis, Escherichia coli - metabolism, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Knockout, Microcirculation, Neonates, Neurons - metabolism, Pathogenesis, Penetration, Proteins, Rats, Rats, Sprague-Dawley, Rodents, Virulence, Virulence factors