E. coli invasion of brain microvascular endothelial cells as a pathogenetic basis of meningitis.
A major limitation to advances in prevention and therapy of bacterial meningitis is our incomplete understanding of the pathogenesis of this disease. Successful isolation and cultivation of BMEC, which constitute the blood brain barrier, and the development of experimental hematogenous meningitis animal model, which mimics closely the pathogenesis of human meningitis, enabled us to dissect the pathogenetic mechanisms of bacterial meningitis. We have shown for the first time using E. coli as a paradigm the mechanisms of bacterial crossing of the blood-brain barrier into the central nervous system. We have shown that invasion of BMEC is a requirement for E. coli K1 crossing of the blood-brain barrier in vivo (Prasadarao et al., 1996b; Huang et al., 1995). We have identified several novel E. coli proteins (i.e., Ibe10, Ibe7, and Ibe23) contributing to invasion of BMEC. We have also established a novel phenotype, i.e., invasion of BMEC, of a well known major E. coli protein, OmpA. In addition, we have shown that some of these E. coli proteins (i.e., OmpA, Ibe10) interact with novel endothelial receptors present on BMEC, not on systemic vascular endothelial cells. Further understanding and characterization of these E. coli-BMEC interactions should allow us to develop novel strategies to prevent this serious infection. In addition, the in vitro and in vivo models of the blood-brain barrier and the information derived from our study should be beneficial to investigating the pathogenesis of meningitis due to other organisms such as group B streptococci, Listeria monocytogenes, Streptococcus pneumoniae and Citrobacter.
Kim
K S
KS
USC School of Medicine and Head, Division of Infectious Diseases, Childrens Hospital Los Angeles, CA 90027, USA.
D000818:Animals; D001921:Brain / Q000098:blood supply*; D004730:Endothelium, Vascular / Q000382:microbiology*; D004926:Escherichia coli / Q000472:pathogenicity*; D006801:Humans; D020814:Meningitis, Escherichia coli / Q000382:microbiology*