title: Intracellular survival and replication of Neisseria meningitidis in human brain microvascular endothelial cells.
abstract: To cause meningitis the extracellular pathogen Neisseria meningitidis has to traverse the blood-cerebrospinal fluid (B-CSF) barrier. Postulating a transcellular passage, meningococci (MC) have been shown to adhere to and enter B-CSF barrier forming human brain microvascular endothelial cells (HBMEC). Furthermore, electron microscopy studies demonstrated that intracellular MC reside within membrane-bound compartments, both solitary and in groups. To investigate the ability of MC to survive and replicate intracellularly, prolonged gentamicin protection assays were performed. Encapsulated bacteria were found to survive and, after an initial delay, to replicate within HBMEC, whereas the number of intracellular capsule-deficient mutants decreased continuously. This strongly suggests that the capsule plays a pivotal role in the intracellular survival of MC. Further investigations were initiated to characterise the membrane-bound compartment, the Neisseria-containing vacuole (NCV). Immunfluorescence microscopy studies showed that NCVs interact with the endocytic pathway acquiring the early endosomal marker protein, transferrin receptor (TfR), and the late endosomal/lysosomal marker protein Lamp-1.
authors.affiliation: Institute of Hygiene and Microbiology, University of Wuerzburg, Josef-Schneider-Str. 2/E1, D-97080 Wuerzburg, Germany.
authors.forename: Joanna
authors.initials: J
authors.lastname: Nikulin
authors.forename: Ursula
authors.initials: U
authors.lastname: Panzner
authors.forename: Matthias
authors.initials: M
authors.lastname: Frosch
authors.forename: Alexandra
authors.initials: A
authors.lastname: Schubert-Unkmeir
mesh_terms: D001921:Brain / Q000166:cytology / Q000382:microbiology*; D004261:DNA Replication; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism / Q000382:microbiology*; D006801:Humans; D052118:Lysosomal-Associated Membrane Protein 1 / Q000378:metabolism; D008854:Microscopy, Electron; D009345:Neisseria meningitidis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011990:Receptors, Transferrin / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors
chemical_list: D052118:Lysosomal-Associated Membrane Protein 1; D011990:Receptors, Transferrin