Binding characteristics of S fimbriated Escherichia coli to isolated brain microvascular endothelial cells.
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.
Division of Infectious Diseases, Childrens Hospital of Los Angeles, CA 90027.
M F
MF
Stins
N V
NV
Prasadarao
L
L
Ibric
C A
CA
Wass
P
P
Luckett
K S
KS
Kim
D000818:Animals; D001422:Bacterial Adhesion / Q000502:physiology*; D001921:Brain / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism*; D010861:Fimbriae, Bacterial / Q000378:metabolism*; D006801:Humans; D007785:Lactose / Q000031:analogs & derivatives / Q000378:metabolism; D009154:Mutation; D012794:Sialic Acids / Q000378:metabolism
D012794:Sialic Acids; C000020:N-acetylneuraminoyllactose; D007785:Lactose