Current concepts on Escherichia coli K1 translocation of the blood-brain barrier

Yi Xie, Kee Jun Kim, Kwang Sik Kim

Research output: Contribution to journalShort surveypeer-review

89 Scopus citations

Abstract

The mortality and morbidity associated with neonatal gram-negative meningitis have remained significant despite advances in antimicrobial chemotherapy. Escherichia coli K1 is the most common gram-negative organism causing neonatal meningitis. Our incomplete knowledge of the pathogenesis of this disease is one of the main reasons for this high mortality and morbidity. We have previously established both in vitro and in vivo models of the blood-brain barrier (BBB) using human brain microvascular endothelial cells (HBMEC) and hematogenous meningitis in neonatal rats, respectively. With these in vitro and in vivo models, we have shown that successful crossing of the BBB by circulating E. coli requires a high-degree of bacteremia, E. coli binding to and invasion of HBMEC, and E. coli traversal of the BBB as live bacteria. Our previous studies using TnphoA, signature-tagged mutagenesis and differential fluorescence induction identified several E. coli K1 determinants such as OmpA, Ibe proteins, AslA, TraJ and CNF1 contributing to invasion of HBMEC in vitro and traversal of the blood-brain barrier in vivo. We have shown that some of these determinants interact with specific receptors on HBMEC, suggesting E. coli translocation of the BBB is the result of specific pathogen-host cell interactions. Recent studies using functional genomics techniques have identified additional E. coli K1 factors that contribute to the high degree of bacteremia and HBMEC binding/invasion/transcytosis. In this review, we summarize the current knowledge on the mechanisms underlying the successful E. coli translocation of the BBB.

Original languageEnglish (US)
Pages (from-to)271-279
Number of pages9
JournalFEMS Immunology and Medical Microbiology
Volume42
Issue number3
DOIs
StatePublished - Nov 1 2004

Keywords

  • Blood-brain barrier
  • Escherichia coli K1
  • Human brain microvascular endothelial cells
  • Meningitis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Microbiology
  • Immunology
  • Microbiology (medical)
  • Infectious Diseases

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