Systematic analyses of signal transduction systems on GltT-GltM glutamate transporter mediated invasion into the host cell in Neisseria meningitidis

2014 Fiscal Year Final Research Report

• Project/Area Number: 24590545
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Bacteriology (including Mycology)
• Research Institution: National Institute of Infectious Diseases
• Principal Investigator: TAKAHASHI Hideyuki 国立感染症研究所, その他部局等, 研究員 (60321866)
• Co-Investigator(Renkei-kenkyūsha): YANAGISAWA Tatsuo 理化学研究所, 横山構造生物学教室, 研究員 (10450420)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 髄膜炎菌 / Neisseria meningitidis / グルタミン酸 / トランスポーター / 細胞侵入

Outline of Final Research Achievements

We found that, 1) the ΔgltT-ΔgltM invasion defect in assay medium (AM) was alleviated in AM without 10% FBS [AM(-S)], 2) the alleviation disappeared again in AM(-S) supplemented with 500 μM glutamate, 3) glutamate uptake by the ΔgltT-ΔgltM mutant was less efficient than that by the wild type strain, 4) both the GltT-GltM-dependent invasion and accumulation of ezrin were more pronounced when N. meningitidis formed larger colonies on human brain microvasocular endothelial cells (HBMEC). These results suggested that GltT-GltM-dependent meningococcal internalization into HBMEC might be induced by the reduced environmental glutamate concentration upon infection. We also found that the amount of glutathione within the ΔgltT-ΔgltM mutant was much lower than that within the wild type Ν. meningitidis strain only upon HBMEC infection, and was correlated with intracellular survival, showing that L-glutamate uptake via GltT-GltM plays multiple roles.

Free Research Field

細菌学、分子生物学