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Staphylococcus aureus FhuD2 Is Involved in the Early Phase of Staphylococcal Dissemination and Generates Protective Immunity in Mice

2012; Oxford University Press; Volume: 206; Issue: 7 Linguagem: Inglês

10.1093/infdis/jis463

1537-6613

Ravi P.N. Mishra, Paolo Mariotti, Luigi Fiaschi, Sarah Nosari, Silvia Maccari, Sabrina Liberatori, Maria Rita Fontana, Alfredo Pezzicoli, Maria Grazia De Falco, Fabiana Falugi, Emrah Altındiş, Davide Serruto, Guido Grandi, Fábio Bagnoli,

Bacterial Infections and Vaccines

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.