title: Identification of genes from the fungal pathogen Cryptococcus neoformans related to transmigration into the central nervous system.
abstract: BACKGROUND
  A mouse brain transmigration assessment (MBTA) was created to investigate the central nervous system (CNS) pathogenesis of cryptococcal meningoencephalitis.
  
  
  RESULTS
  Two cryptococcal mutants were identified from a pool of 109 pre-selected mutants that were signature-tagged with the nourseothricin acetyltransferase (NAT) resistance cassette. These two mutants displayed abnormal transmigration into the central nervous system. One mutant displaying decreased transmigration contains a null mutation in the putative FNX1 gene, whereas the other mutant possessing a null mutation in the putative RUB1 gene exhibited increased transmigration into the brain. Two macrophage adhesion-defective mutants in the pool, 12F1 and 3C9, showed reduced phagocytosis by macrophages, but displayed no defects in CNS entry suggesting that transit within macrophages (the "Trojan horse" model of CNS entry) is not the primary mechanism for C. neoformans migration into the CNS in this MBTA.
  
  
  CONCLUSIONS
  This research design provides a new strategy for genetic impact studies on how Cryptococcus passes through the blood-brain barrier (BBB), and the specific isolated mutants in this assay support a transcellular mechanism of CNS entry.
authors.affiliation: Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Hsiang-Kuang
authors.initials: HK
authors.lastname: Tseng
authors.forename: Chang-Pan
authors.initials: CP
authors.lastname: Liu
authors.forename: Michael S
authors.initials: MS
authors.lastname: Price
authors.forename: Ambrose Y
authors.initials: AY
authors.lastname: Jong
authors.forename: Jui-Chih
authors.initials: JC
authors.lastname: Chang
authors.forename: Dena L
authors.initials: DL
authors.lastname: Toffaletti
authors.forename: Marisol
authors.initials: M
authors.lastname: Betancourt-Quiroz
authors.forename: Aubrey E
authors.initials: AE
authors.lastname: Frazzitta
authors.forename: Wen-Long
authors.initials: WL
authors.lastname: Cho
authors.forename: John R
authors.initials: JR
authors.lastname: Perfect
mesh_terms: D000123:Acetyltransferases / Q000378:metabolism; D000818:Animals; D001812:Blood-Brain Barrier / Q000382:microbiology; D002448:Cell Adhesion; D002490:Central Nervous System / Q000166:cytology* / Q000382:microbiology*; D003455:Cryptococcus neoformans / Q000235:genetics* / Q000254:growth & development / Q000502:physiology*; D042783:Endothelial Cells / Q000166:cytology / Q000382:microbiology; D005800:Genes, Fungal / Q000235:genetics*; D056726:Genetic Association Studies; D005820:Genetic Testing; D051379:Mice; D055806:Microvessels / Q000166:cytology; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D016133:Polymerase Chain Reaction; D015203:Reproducibility of Results; D013696:Temperature; D057900:Transcytosis; D057705:Transendothelial and Transepithelial Migration / Q000235:genetics*
chemical_list: D000123:Acetyltransferases; C050473:nourseothricin acetyltransferase