E. coli Invasion of Brain Microvascular Endothelial Cells as a Pathogenetic Basis of Meningitis

  • Kwang Sik Kim
Part of the Subcellular Biochemistry book series (SCBI, volume 33)


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.


Focal Adhesion Kinase Human Umbilical Vein Endothelial Cell Bacterial Meningitis Brain Microvascular Endothelial Cell Human Brain Microvascular Endothelial Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Badger, J.L., and Kim, K.S., 1998, Environmental growth conditions influence the ability of E. coli K1 to invade brain microvascular endothelial cells and confer serum resistance, Infect. Immun. 66: 5692–5697.PubMedGoogle Scholar
  2. Durand, M.L., Calderwood, S.B., Weber, D.J., Miller, S.I., Southwick, F.S., Caviness, V.S. Jr, and Swartz, M.N., 1993, Acute bacterial meningitis in adults. A review of 493 episodes, N. Engl. J. Med. 328: 21–28.PubMedCrossRefGoogle Scholar
  3. 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
  4. Kim, K.S., 1985, Comparison of cefotaxime, imipenem-cilastatin, ampicillin-gentamicin and ampicillin-chloramphenicol in the treatement of experimental Escherichia coli bacteremia and meningitis, Antimicrob. Agents Chemother. 28: 433–436.PubMedCrossRefGoogle Scholar
  5. Kim, K.S., Itabashi, H., Gemski, P., Sadoff, J., Warren, R.L., and Cross, A.S., 1992, The K1 capsule is the critical determinant in the development of Escherichia coli meningitis in the rat, J. Clin. Invest. 90: 897–905.PubMedCrossRefGoogle Scholar
  6. 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
  7. Nizet, V., Kim, K.S., Stins, M., Jonas, M., Nguyen, D., and Rubens, C.E., 1997, Invasion of brain microvascular endothelial cells by group B stretococci, Infect. Immun. 65: 5074–5081.PubMedGoogle Scholar
  8. Prasadarao, N.V., Wass, C.A., and Kim, K.S., 1996a, Endothelial cell GIcNAcß1–4 GIcNAc epitopes for outer membrane protein A traversal of E. coli across the blood-brain barrier, Infect. Immun. 64: 154–160.PubMedGoogle Scholar
  9. Prasadarao, N.V., Wass, C., Stins, M.F., Weiser, J., Huang, S.H., and Kim, K.S., 1996b, Outer membrane protein A of E. coli contributes to invasion of brain microvascular endothelial cells, Infect. Immun. 64: 146–153.PubMedGoogle Scholar
  10. 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
  11. Prasadarao, N.V., Wass, C.A., and Kim, K.S., 1997, Identification and characterization of Sfimbriae binding sialoglycoproteins on brain microvascular endothelial cells, Infect. Immun. 65: 2852–2860.PubMedGoogle Scholar
  12. Stins, M.F., Gilles, E, and Kim, K.S., 1997, Selective expression of adhesion molecules on human brain microvascular endothelial cells, J. Neuroimmunol. 76: 81–90.PubMedCrossRefGoogle Scholar
  13. 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
  14. Unhanand, M., Musatafa, M.M., McCracken, G.H., and Nelso, J.D., 1993, Gram-negative enteric bacillary meningitis: A twenty-one year experience, J. Pediatr. 122: 15–21.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2000

Authors and Affiliations

  • Kwang Sik Kim
    • 1
  1. 1.Division of Infectious DiseasesChildrens Hospital Los AngelesLos AngelesUSA

Personalised recommendations