title: The Dps-like protein Fri of Listeria monocytogenes promotes stress tolerance and intracellular multiplication in macrophage-like cells.
abstract: Members of the ferritin-like Dps protein family are found in a number of bacterial species, where they demonstrate the potential to bind iron, and have been implicated in tolerance to oxidative stress. In this study of the food-borne pathogen Listeria monocytogenes, the fri gene encoding a Dps homologue was deleted, and, compared to wild-type cells, it was found that the resulting mutant was less resistant to hydrogen peroxide, and demonstrated reduced survival following long-term (7-11 days) incubation in laboratory media. In view of this, it is shown that fri gene expression is controlled by the hydrogen peroxide regulator PerR, as well as the general stress sigma factor sigmaB. When fri mutant cells were transferred to iron-limiting conditions, growth was retarded relative to wild-type cells, indicating that Fri may be required for iron storage. This notion is supported by the observation that the L. monocytogenes genome appears not to encode other ferritin-like proteins. Given the role of Fri in resistance to oxidative stress, and growth under iron-limiting conditions, the ability of the fri mutant to infect mice was examined. When injected by the intraperitoneal route, the fri mutant demonstrated a reduced capacity to proliferate in the organs of infected mice relative to the wild-type, whereas when the bacteria were supplied intravenously this effect was mitigated. In addition, the mutant was impaired in its ability to survive and grow in J774.A1 mouse macrophage cells. Thus, the data suggest that Fri contributes to the ability of L. monocytogenes to survive in environments where oxidative stress and low iron availability may impede bacterial proliferation.
authors.affiliation: Department of Veterinary Pathobiology, Royal Veterinary and Agricultural University (KVL), Stigbøjlen 4, DK-1870 Frederiksberg C, Denmark.
authors.forename: Katja N
authors.initials: KN
authors.lastname: Olsen
authors.affiliation: Department of Veterinary Pathobiology, Royal Veterinary and Agricultural University (KVL), Stigbøjlen 4, DK-1870 Frederiksberg C, Denmark.
authors.forename: Marianne H
authors.initials: MH
authors.lastname: Larsen
authors.affiliation: Department of Microbiology and National Food Biotechnology Centre, University College Cork, Cork, Ireland.
authors.forename: Cormac G M
authors.initials: CGM
authors.lastname: Gahan
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Southern Denmark, Campusvej 55, DK-5230 Odense M, Denmark.
authors.forename: Birgitte
authors.initials: B
authors.lastname: Kallipolitis
authors.affiliation: Department of Veterinary Pathobiology, Royal Veterinary and Agricultural University (KVL), Stigbøjlen 4, DK-1870 Frederiksberg C, Denmark.
authors.forename: Xenia A
authors.initials: XA
authors.lastname: Wolf
authors.affiliation: Department of Microbiology and National Food Biotechnology Centre, University College Cork, Cork, Ireland.
authors.forename: Rosemary
authors.initials: R
authors.lastname: Rea
authors.affiliation: Department of Microbiology and National Food Biotechnology Centre, University College Cork, Cork, Ireland.
authors.forename: Colin
authors.initials: C
authors.lastname: Hill
authors.affiliation: Department of Veterinary Pathobiology, Royal Veterinary and Agricultural University (KVL), Stigbøjlen 4, DK-1870 Frederiksberg C, Denmark.
authors.forename: Hanne
authors.initials: H
authors.lastname: Ingmer
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005293:Ferritins / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D018869:Heat-Shock Response; D007501:Iron / Q000378:metabolism; D008089:Listeria monocytogenes / Q000235:genetics / Q000254:growth & development / Q000472:pathogenicity* / Q000502:physiology; D008264:Macrophages / Q000382:microbiology*; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation
chemical_list: D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; C083911:DPS protein, Bacteria; D005293:Ferritins; D007501:Iron