Neisseria meningitidis accelerates ferritin degradation in host epithelial cells to yield an essential iron source.
In order to colonize humans and cause disease, pathogenic bacteria must assimilate iron from their host. The vast majority of non-haem iron in humans is localized intracellularly, within the storage molecule ferritin. Despite the vast reserves of iron within ferritin, no pathogen has been demonstrated previously to exploit this molecule as an iron source. Here, we show that the Gram-negative diplococcus Neisseria meningitidis can trigger rapid redistribution and degradation of cytosolic ferritin within infected epithelial cells. Indirect immunofluorescence microscopy revealed that cytosolic ferritin is aggregated and recruited to intracellular meningococci (MC). The half-life of ferritin within cultured epithelial cells was found to decrease from 20.1 to 5.3 h upon infection with MC. Supplementation of infected epithelial cells with ascorbic acid abolished ferritin redistribution and degradation and prevented intracellular MC from replicating. The lysosomal protease inhibitor leupeptin slowed ferritin turnover and also retarded MC replication. Our laboratory has shown recently that MC can interfere with transferrin uptake by infected cells (Bonnah R.A., et al., 2000, Cell Microbiol 2: 207-218) and that, perhaps as a result, the infected cells have a transcriptional profile indicative of iron starvation (Bonnah, R.A., et al., 2004, Cell Microbiol 6: 473-484). In view of these findings, we suggest that accelerated ferritin degradation occurs as a response to an iron starvation state induced by MC infection and that ferritin degradation provides intracellular MC with a critical source of iron.
Larson
Jason A
JA
Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, OR 97239, USA. larsonja@ohsu.edu
Howie
Heather L
HL
So
Magdalene
M
D002455:Cell Division; D002460:Cell Line; D002584:Cervix Uteri / Q000166:cytology; D002850:Chromatography, Gel; D004847:Epithelial Cells / Q000382:microbiology* / Q000502:physiology; D005260:Female; D005293:Ferritins / Q000235:genetics* / Q000378:metabolism*; D006207:Half-Life; D006801:Humans; D007501:Iron / Q000378:metabolism*; D009345:Neisseria meningitidis / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D012333:RNA, Messenger; D005293:Ferritins; D007501:Iron