Abstract

Escherichia coli is the major Gram-negative bacterial pathogen in neonatal meningitis. Outer membrane protein A (OmpA) is a conserved major protein in the E. coli outer membrane and is involved in several host-cell interactions. To characterize the role of OmpA in the invasion of astrocytes by E. coli, we investigated OmpA-positive and OmpA-negative E. coli strains. Outer membrane protein A E44, E105, and E109 strains adhered to and invaded C6 glioma cells 10- to 15-fold more efficiently than OmpA-negative strains. Actin rearrangement, protein tyrosine kinase, and phosphoinositide 3-kinase activation were required for OmpA-mediated invasion by E. coli. In vitro infection of C6 cells and intracerebral injection into mice of the E44 strain induced expression of the astrocyte differentiation marker glial fibrillary acidic protein and the inflammatory mediators cyclooxygenase 2 and nitric oxide synthase 2. After intracerebral infection with E44, all C57BL/6 mice died within 36hours, whereas 80% of mice injected with E44 premixed with recombinant OmpA protein survived. Astrocyte activation and neutrophil infiltration were reduced in brain tissue sections in the mice given OmpA. Taken together, these data suggest that OmpA-mediated invasion plays an important role in the early stage of E.coli-induced brain damage, and that it may have therapeutic use in E. coli meningitis.

Original languageEnglish
Pages (from-to)677-690
Number of pages14
JournalJournal of Neuropathology and Experimental Neurology
Volume68
Issue number6
DOIs
Publication statusPublished - Jun 2009

Keywords

  • Astrocyte
  • Cyclooxygenase 2
  • Escherichia coli
  • Glial fibrillary acidic protein
  • Nitric oxide synthase 2
  • Outer membrane protein A

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Clinical Neurology
  • Neurology
  • Cellular and Molecular Neuroscience

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