Despite appropriate antibiotics, CNS infections with Escherichia coli continue to cause significant morbidity and mortality. The lack of knowledge concerning the pathogenesis of this infection contributes to limited improvements in interventions. Successful transversal of E. coli across the blood brain barrier requires S. fimbriae for binding and OmpA for invasion. Both of these interact with epitopes (NeuAc alpha 2,3-galactose and G1cNAc beta 1, 4G1cNAc) on a novel 65 Da sialoglycoprotein on brain microvascular endothelium (BMEC). To date, the investigator has been screening a human BMEC cDNA library with antibodies against the 65 Da protein and has identified 6 positive cDNA clones. The goals of the current proposal are to 1) characterize the gene encoding the 65 Da glycoprotein involved with E. coli binding 2) to use recombinant protein to further investigate bacteria (host interactions in transfected CHO cells and in blocking experiments in a rat meningitis model and 3) to determine if E. coli binding and invasion of BMEC is due to the glycoprotein by using anti-sense oligonucleotides to inhibit gene expression in BMEC.
Showing the most recent 10 out of 39 publications
