OmpA is the critical component for Escherichia coli invasion-induced astrocyte activation.
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.
Wu
Hsueh-Hsia
HH
Graduate Institute and Department of Microbiology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Yang
Yi-Yuan
YY
Hsieh
Wen-Shyang
WS
Lee
Chi-Hsin
CH
Leu
Sy-Jye C
SJ
Chen
Mei-Ru
MR
D000199:Actins / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000382:microbiology* / Q000502:physiology; D001425:Bacterial Outer Membrane Proteins / Q000502:physiology*; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004926:Escherichia coli / Q000472:pathogenicity*; D004927:Escherichia coli Infections / Q000382:microbiology* / Q000401:mortality / Q000473:pathology*; D029968:Escherichia coli Proteins / Q000502:physiology; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005910:Glioma; D051379:Mice; D008810:Mice, Inbred C57BL; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000502:physiology; D016019:Survival Analysis; D013997:Time Factors
D000199:Actins; D001425:Bacterial Outer Membrane Proteins; D029968:Escherichia coli Proteins; D005904:Glial Fibrillary Acidic Protein; C078167:OMPA outer membrane proteins; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D051546:Cyclooxygenase 2; D010751:Phosphopyruvate Hydratase