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American Journal of Pathology, Vol 145, 1228-1236, Copyright © 1994 by American Society for Investigative Pathology
REGULAR ARTICLES |
MF Stins, NV Prasadarao, L Ibric, CA Wass, P Luckett and KS Kim
Division of Infectious Diseases, Childrens Hospital of Los Angeles, CA 90027.
To assess the role of S fimbriae in the pathogenesis of Escherichia coli meningitis, transformants of E. coli strains with or without S fimbriae plasmid were compared for their binding to microvessel endothelial cells isolated from bovine brain cortices (BMEC). The BMEC's displayed a cobblestone appearance, were positive for factor VIII, carbonic anhydrase IV, took up fluorescent-labeled acetylated low density lipoprotein, and exhibited gamma glutamyl transpeptidase activity. Binding of S fimbriated E. coli to BMEC was approximately threefold greater than nonfimbriated E. coli Similarly S fimbriated E. coli bound to human brain endothelial cells approximately threefold greater than nonfimbriated E. coli. Binding was reduced approximately 60% by isolated S fimbriae and about 80% by anti-S adhesin antibody. Mutating the S adhesin gene resulted in a complete loss of the binding, whereas mutagenesis of the major S fimbriae subunit gene sfaA did not significantly affect binding. Pretreatment of BMEC with neuraminidase or prior incubation of S fimbriated E. coli with NeuAc alpha 2,3-sialyl lactose completely abolished binding. These findings indicate that S fimbriated E. coli bind to NeuAc alpha 2,3-galactose containing glycoproteins on brain endothelial cells via a lectin-like activity of SfaS adhesin. This might be an important early step in the penetration of bacteria across the blood-brain barrier in the development of E. coli meningitis.
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N. V. Prasadarao, C. A. Wass, M. F. Stins, H. Shimada, and K. S. Kim Outer Membrane Protein A-Promoted Actin Condensation of Brain Microvascular Endothelial Cells Is Required for Escherichia coli Invasion Infect. Immun., November 1, 1999; 67(11): 5775 - 5783. [Abstract] [Full Text] [PDF]
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L. Greiffenberg, W. Goebel, K. S. Kim, I. Weiglein, A. Bubert, F. Engelbrecht, M. Stins, and M. Kuhn Interaction of Listeria monocytogenes with Human Brain Microvascular Endothelial Cells: InlB-Dependent Invasion, Long-Term Intracellular Growth, and Spread from Macrophages to Endothelial Cells Infect. Immun., November 1, 1998; 66(11): 5260 - 5267. [Abstract] [Full Text] [PDF]
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