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.