title: A mutant in the Listeria monocytogenes Fur-regulated virulence locus (frvA) induces cellular immunity and confers protection against listeriosis in mice.
abstract: Listeria monocytogenes is a Gram-positive intracellular pathogen that is responsible for listeriosis, a potentially fatal, food-borne illness. Due to its cytoplasmic location during infection, this pathogen can mediate a long-lasting cellular immune response, which makes attenuated strains strong candidates for vaccine development. Recently, our group identified and characterized frvA (Fur-regulated virulence factor A), and deletion of this gene resulted in disruption of iron homeostasis and a strong attenuation in virulence. Despite significant attenuation in the mouse infection model, the frvA mutant was capable of intracellular growth in antigen-presenting cells. Indeed, mice immunized with L. monocytogenes ΔfrvA were able to effectively stimulate specific CD8(+) T cells to the listerial epitopes LLO(91-99) and P60(217-225) at levels comparable with L. monocytogenes strain EGDe. Most notably, mice immunized with ΔfrvA then subsequently challenged with the wild-type strain were completely protected from listerial infection. On the basis of these results, we advocate the use of ΔfrvA as a live attenuated listerial vaccine, and propose that this mutant may serve as a platform for the development of a future vaccine delivery vehicle.
authors.affiliation: Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland.|Department of Microbiology, University College Cork, Cork, Ireland.
authors.forename: Heather P
authors.initials: HP
authors.lastname: McLaughlin
authors.affiliation: Department of Pharmaceutical Microbiology, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt.|School of Pharmacy, University College Cork, Cork, Ireland.|Department of Microbiology, University College Cork, Cork, Ireland.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Bahey-El-Din
authors.affiliation: Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland.|Department of Microbiology, University College Cork, Cork, Ireland.
authors.forename: Pat G
authors.initials: PG
authors.lastname: Casey
authors.affiliation: Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland.|Department of Microbiology, University College Cork, Cork, Ireland.
authors.forename: Colin
authors.initials: C
authors.lastname: Hill
authors.affiliation: School of Pharmacy, University College Cork, Cork, Ireland.|Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland.|Department of Microbiology, University College Cork, Cork, Ireland.
authors.forename: Cormac G M
authors.initials: CGM
authors.lastname: Gahan
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000382:microbiology; D001426:Bacterial Proteins / Q000235:genetics*; D001428:Bacterial Vaccines / Q000276:immunology; D001769:Blood / Q000382:microbiology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D005260:Female; D006801:Humans; D007501:Iron / Q000378:metabolism; D008089:Listeria monocytogenes / Q000235:genetics* / Q000254:growth & development / Q000276:immunology* / Q000472:pathogenicity; D008088:Listeriosis / Q000276:immunology* / Q000382:microbiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation
chemical_list: D001426:Bacterial Proteins; D001428:Bacterial Vaccines; D000939:Epitopes; D007501:Iron