Human monoclonal antibodies against Staphylococcus aureus surface antigens recognize in vitro and in vivo biofilm

抗金黄色葡萄球菌表面抗原的人类单克隆抗体识别体外和体内生物膜

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作者:Lisanne de Vor #, Bruce van Dijk #, Kok van Kessel, Jeffrey S Kavanaugh, Carla de Haas, Piet C Aerts, Marco C Viveen, Edwin C Boel, Ad C Fluit, Jakub M Kwiecinski, Gerard C Krijger, Ruud M Ramakers, Freek J Beekman, Ekaterina Dadachova, Marnix Geh Lam, H Charles Vogely, Bart Ch van der Wal, Jos Ag v

Abstract

Implant-associated Staphylococcus aureus infections are difficult to treat because of biofilm formation. Bacteria in a biofilm are often insensitive to antibiotics and host immunity. Monoclonal antibodies (mAbs) could provide an alternative approach to improve the diagnosis and potential treatment of biofilm-related infections. Here, we show that mAbs targeting common surface components of S. aureus can recognize clinically relevant biofilm types. The mAbs were also shown to bind a collection of clinical isolates derived from different biofilm-associated infections (endocarditis, prosthetic joint, catheter). We identify two groups of antibodies: one group that uniquely binds S. aureus in biofilm state and one that recognizes S. aureus in both biofilm and planktonic state. Furthermore, we show that a mAb recognizing wall teichoic acid (clone 4497) specifically localizes to a subcutaneously implanted pre-colonized catheter in mice. In conclusion, we demonstrate the capacity of several human mAbs to detect S. aureus biofilms in vitro and in vivo.

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