E. coli Invasion of Brain Microvascular Endothelial Cells as a Pathogenetic Basis of Meningitis
Bacterial meningitis still results in a high mortality and morbidity despite advances in antimicrobial chemotheraphy and supportive care (Durand et al., 1993; Unhanand et al., 1993). Both clinical and experimental data indicate limited efficacy with antimicrobial chemotherapy alone (Kim, 1985; McCracken et al., 1984). A major contributing factor is the incomplete understanding of the pathogenesis and pathophysiology associated with the bacterial meningitis. For example, most cases of bacterial meningitis develop as a result of hematogenous spread, but it is not clear how circulating bacteria cross the blood-brain barrier. We have utilized E.coli as a paradigm to examine how circulating bacteria traverse the blood-brain barrier. In addition, E. coli is the most common gram-negative bacterium that causes meningitis, particularly during the neonatal period. Our investigations have become feasible with the availability of both in vitro and in vivo models of the blood-brain barrier.
KeywordsFocal Adhesion Kinase Human Umbilical Vein Endothelial Cell Bacterial Meningitis Brain Microvascular Endothelial Cell Human Brain Microvascular Endothelial Cell
Unable to display preview. Download preview PDF.
- Huang, S.H., Wass, C.A., Fu, Q., Prasadarao, N.V., Stins, M., and Kim, K.S, 1995, E. coli invasion of brain microvascular endothelial cells in vitro and in vivo: Molecular cloning and characterization of E. coli invasion gene ibe10, Infect. Immun. 63: 4470–4475.Google Scholar
- McCracken, G.H. Jr., Threlkeld, N., Mize, S., Baker, C.J., Kapal, S.L., Fraingezicht, I., Feldman, W.F., and Schad, U., The Neonatal Meningitis Cooperative Study Group, 1984, Moxalactam therapy for neonatal meningitis due to gram-negative sepsis enteric bacilli, DAMA 252: 1427–1437.Google Scholar
- Prasadarao, N.Y., Huang, S.H., Wass, C.A., and Kim, K.S., 1999, Identification and characterization of a novel Ibe10 binding protein on brain microvascular endothelial cells contributing to E. coli invasion, Infect. Immun. (In press).Google Scholar
- Stins, M.F., Prasadarao, N.V., Ibric, L., Wass, C.A., Luckett, P., and Kim, K.S., 1994, Binding characteristics of S-fimbriated Escherichia coli to isolated brain microvascular endothelial cells, Amer. J. Pathol. 145: 1228–1236.Google Scholar