title: Staphylococcus aureus FhuD2 is involved in the early phase of staphylococcal dissemination and generates protective immunity in mice.
abstract: Iron availability plays an essential role in staphylococcal pathogenesis. We selected FhuD2, a lipoprotein involved in iron-hydroxamate uptake, as a novel vaccine candidate against Staphylococcus aureus. Unprecedented for staphylococcal lipoproteins, the protein was demonstrated to have a discrete, punctate localization on the bacterial surface. FhuD2 vaccination generated protective immunity against diverse clinical S. aureus isolates in murine infection models. Protection appeared to be associated with functional antibodies that were shown to mediate opsonophagocytosis, to be effective in passive transfer experiments, and to potentially block FhuD2-mediated siderophore uptake. Furthermore, the protein was found to be up-regulated in infected tissues and was required for staphylococcal dissemination and abscess formation. Herein we show that the staphylococcal iron-hydroxamate uptake system is important in invasive infection and functions as an efficacious vaccine target.
authors: Novartis Vaccines,  Research Center, Siena,  Italy.
authors: Ravi P N
authors: RP
authors: Mishra
authors: Paolo
authors: P
authors: Mariotti
authors: Luigi
authors: L
authors: Fiaschi
authors: Sarah
authors: S
authors: Nosari
authors: Silvia
authors: S
authors: Maccari
authors: Sabrina
authors: S
authors: Liberatori
authors: Maria Rita
authors: MR
authors: Fontana
authors: Alfredo
authors: A
authors: Pezzicoli
authors: Maria Grazia
authors: MG
authors: De Falco
authors: Fabiana
authors: F
authors: Falugi
authors: Emrah
authors: E
authors: Altindis
authors: Davide
authors: D
authors: Serruto
authors: Guido
authors: G
authors: Grandi
authors: Fabio
authors: F
authors: Bagnoli
mesh_terms: D000038:Abscess / Q000276:immunology / Q000517:prevention & control; D000595:Amino Acid Sequence; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D005290:Ferric Compounds / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D055786:Gene Knockout Techniques; D018922:HL-60 Cells; D006801:Humans; D006877:Hydroxamic Acids / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D021381:Protein Transport; D011817:Rabbits; D018805:Sepsis / Q000276:immunology / Q000517:prevention & control; D013203:Staphylococcal Infections / Q000276:immunology / Q000517:prevention & control*; D013209:Staphylococcal Vaccines / Q000008:administration & dosage; D013211:Staphylococcus aureus / Q000254:growth & development / Q000276:immunology / Q000378:metabolism*; D014611:Vaccination
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D005290:Ferric Compounds; D006877:Hydroxamic Acids; D026901:Membrane Transport Proteins; D013209:Staphylococcal Vaccines; C074579:iron (III) hydroxamate