OmpA is the critical component for escherichia coli invasion-induced astrocyte activation

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

UR - http://www.scopus.com/inward/record.url?scp=67649389709&partnerID=8YFLogxK

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 - American Journal of Psychotherapy

JF - American Journal of Psychotherapy

SN - 0002-9564

IS - 6

ER -