Fibronectin mediates Opc-dependent internalization of Neisseria meningitidis in human brain microvascular endothelial cells

Alexandra Unkmeir, Kirsten Latsch, Guido Dietrich, Eva Wintermeyer, Birgitta Schinke, Stefan Schwender, Kwang Sik Kim, Martin Eigenthaler, Matthias Frosch

Research output: Contribution to journalArticle

Abstract

A central step in the pathogenesis of bacterial meningitis caused by Neisseria meningitidis (the meningococcus) is the interaction of the bacteria with cells of the blood-brain barrier. In the present study, we analysed the invasive potential of two strains representing hypervirulent meningococcal lineages of the ET-5 and ET-37 complex in human brain-derived endothelial cells (HBEMCs). In contrast to previous observations made with epithelial cells and human umbilical vein-derived endothelial cells (HUVECs), significant internalization of encapsulated meningococci by HBMECs was observed. However, this uptake was found only for the ET-5 complex isolate MC58, and not for an ET-37 complex strain. Furthermore, the uptake of meningococci by HBMECs depended on the presence of human serum, whereas serum of bovine origin did not promote the internalization of meningococci in HBMECs. By mutagenesis experiments, we demonstrate that internalization depended on the expression of the opc gene, which is present in meningococci of the ET-5 complex, but absent in ET-37 complex meningococci. Chromatographic separation of human serum proteins revealed fibronectin as the uptake-promoting serum factor, which binds to HBMECs via α5β1 integrin receptors. These data provide evidence for unique molecular mechanisms of the interaction of meningococci with endothelial cells of the blood-brain barrier and contribute to our understanding of the pathogenesis of meningitis caused by meningococci of different clonal lineages.

Original languageEnglish (US)
Pages (from-to)933-946
Number of pages14
JournalMolecular Microbiology
Volume46
Issue number4
DOIs
StatePublished - 2002

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Neisseria meningitidis
Fibronectins
Endothelial Cells
Brain
Blood-Brain Barrier
Serum
Bacterial Meningitides
Human Umbilical Vein Endothelial Cells
Meningitis
Integrins
Mutagenesis
Blood Proteins
Epithelial Cells
Bacteria
Gene Expression

ASJC Scopus subject areas

  • Molecular Biology
  • Microbiology

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Fibronectin mediates Opc-dependent internalization of Neisseria meningitidis in human brain microvascular endothelial cells. / Unkmeir, Alexandra; Latsch, Kirsten; Dietrich, Guido; Wintermeyer, Eva; Schinke, Birgitta; Schwender, Stefan; Kim, Kwang Sik; Eigenthaler, Martin; Frosch, Matthias.

In: Molecular Microbiology, Vol. 46, No. 4, 2002, p. 933-946.

Research output: Contribution to journalArticle

Unkmeir, A, Latsch, K, Dietrich, G, Wintermeyer, E, Schinke, B, Schwender, S, Kim, KS, Eigenthaler, M & Frosch, M 2002, 'Fibronectin mediates Opc-dependent internalization of Neisseria meningitidis in human brain microvascular endothelial cells', Molecular Microbiology, vol. 46, no. 4, pp. 933-946. https://doi.org/10.1046/j.1365-2958.2002.03222.x
Unkmeir, Alexandra ; Latsch, Kirsten ; Dietrich, Guido ; Wintermeyer, Eva ; Schinke, Birgitta ; Schwender, Stefan ; Kim, Kwang Sik ; Eigenthaler, Martin ; Frosch, Matthias. / Fibronectin mediates Opc-dependent internalization of Neisseria meningitidis in human brain microvascular endothelial cells. In: Molecular Microbiology. 2002 ; Vol. 46, No. 4. pp. 933-946.
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