Multiple Functions of Glutamate Uptake via Meningococcal GltT-GltM l-Glutamate ABC Transporter in Neisseria meningitidis Internalization into Human Brain Microvascular Endothelial Cells
We previously reported thatNeisseria meningitidisinternalization into human brain microvasocular endothelial cells (HBMEC) was triggered by the influx of extracellularl-glutamate via the GltT-GltMl-glutamate ABC transporter, but the underlying mechanism remained unclear. We found that the ΔgltTΔgltMinvasion 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 ΔgltTΔgltMmutant 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 whenN. meningitidisformed 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 ΔgltTΔgltMmutant was much lower than that within the wild-typeN. meningitidisstrain only upon HBMEC infection and was correlated with intracellular survival. Considering that thel-glutamate obtained via GltT-GltM is utilized as a nutrient in host cells,l-glutamate uptake via GltT-GltM plays multiple roles inN. meningitidisinternalization into HBMEC.