TY - JOUR
T1 - OmpA is the critical component for escherichia coli invasion-induced astrocyte activation
AU - Wu, Hsueh Hsia
AU - Yang, Yi Yuan
AU - Hsieh, Wen Shyang
AU - Lee, Chi Hsin
AU - Leu, Sy Jye C
AU - Chen, Mei Ru
PY - 2009/6
Y1 - 2009/6
N2 - 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.
AB - 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.
KW - Astrocyte
KW - Cyclooxygenase 2
KW - Escherichia coli
KW - Glial fibrillary acidic protein
KW - Nitric oxide synthase 2
KW - Outer membrane protein A
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UR - http://www.scopus.com/inward/citedby.url?scp=67649389709&partnerID=8YFLogxK
U2 - 10.1097/NEN.0b013e3181a77d1e
DO - 10.1097/NEN.0b013e3181a77d1e
M3 - Article
C2 - 19458541
AN - SCOPUS:67649389709
VL - 68
SP - 677
EP - 690
JO - Journal of Psychotherapy Practice and Research
JF - Journal of Psychotherapy Practice and Research
SN - 0002-9564
IS - 6
ER -