Multiple functions of glutamate uptake via meningococcal GltT-GltM L-glutamate ABC transporter in Neisseria meningitidis internalization into human brain microvascular endothelial cells

Hideyuki Takahashi, Tatsuo Yanagisawa, Kwang Sik Kim, Shigeyuki Yokoyama, Makoto Ohnishi

Research output: Contribution to journalArticlepeer-review

Abstract

We previously reported that Neisseria meningitidis internalization into human brain microvasocular endothelial cells (HBMEC) was triggered by the influx of extracellular L-glutamate via the GltT-GltM L-glutamate ABC transporter, but the underlying mechanism remained unclear. We found that the ΔgltT ΔgltM invasion defect in assay medium (AM) was alleviated in AM without 10% fetal bovine serum (FBS) [AM(-S)]. The alleviation disappeared again in AM(-S) supplemented with 500 μM glutamate. Glutamate uptake by the ΔgltT ΔgltM mutant was less efficient than that by the wild-type strain, but only upon HBMEC infection. We also observed that both GltT-GltM-dependent invasion and accumulation of ezrin, a key membrane-cytoskeleton linker, were more pronounced when N. meningitidis formed larger colonies on HBMEC under physiological glutamate conditions. These results suggested that GltT-GltM-dependent meningococcal internalization into HBMEC might be induced by the reduced environmental glutamate concentration upon infection. Furthermore, we found that the amount of glutathione within the ΔgltT ΔgltM mutant was much lower than that within the wild-type N. meningitidis strain only upon HBMEC infection and was correlated with intracellular survival. Considering that the L-glutamate obtained via GltT-GltM is utilized as a nutrient in host cells, L-glutamate uptake via GltT-GltM plays multiple roles in N. meningitidis internalization into HBMEC.

Original languageEnglish (US)
Pages (from-to)3555-3567
Number of pages13
JournalInfection and immunity
Volume83
Issue number9
DOIs
StatePublished - 2015

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

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