The biofilm matrix exoproteome as an effective multicomponent vaccine against S. aureus biofilm -­‐ associated infections Carmen Gil 1 , Jaione Valle 1 , Cristina Latasa 1 , Saioa Burgui 1 , Alejandro Toledo -­‐ Arana 1 , Cristina Solano 1 and Iñigo L asa 1 1 Laboratory of M icrobial Bio fil ms, Inst ituto de Agrobiotecnología, IdAB , Universidad Pública de Navarra -­‐ CSIC -­‐ Gobierno de Navarra, Pamplona, Spain. The S. aureus biofilm mode of growth is associated with several chronic infections such as rhinosinusitis, subclinical masti t is, wound infections, keratitis and osteomyelitis . Thus, a great effort is being made in order to obtain an effective vaccine against this pathogenic bacterium. However, most of these efforts have been focused in the identification of antigens expressed u nder planktonic conditions ignoring the biofilm life style. Given the fact that during a biofilm -­‐ associated infection, the first primary interface between the host and bacteria is the self -­‐ produced extracellular matrix, in this study , we have analyse d the potential of extracellular proteins found in the biofilm matrix as an effective multicomponent vaccine against S. aureus infections. We have used proteomic approaches to characterize the exoproteome specific of the biofilm lifestyle from two clinical S. a ureus isolates . The results showed that S. aureus biofilm matrix exoproteome contains more than 30 extracellular proteins . An extract comprising this exoproteome induce d a humoral immune response in mice . Antibodies against such extract promoted opsonopha gocytosis of S. aureus by J774 murine macrophage cells. Characterization of the cellular response stimulated by biofilm matrix exoproteins demonstrated that they induce the production of IL -­‐ 10 and IL -­‐ 17. Evaluation of this vaccine candidate, using an in vi vo model of mesh -­‐ associated biofilm infection, showed that i mmunization with the biofilm matrix exoproteome significantly reduced the number of bacterial cells inside a biofilm and on the surrounding tissue and also limited organ colonization. Altogether, these data illustrate the potential of biofilm matrix exoprote ome to protect against S. aureus biofilm -­‐ associated infectio

Trabajo presentado en el 60th Nobel Conference on Biofilm Formation, its Clinical Impact and Potential Treatment, celebrado en Estocolmo del 28 al 30 de agosto de 2013.

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