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

Author:

de Vor Lisanne1ORCID,van Dijk Bruce2,van Kessel Kok1,Kavanaugh Jeffrey S3,de Haas Carla1,Aerts Piet C1,Viveen Marco C1,Boel Edwin C1ORCID,Fluit Ad C1,Kwiecinski Jakub M3ORCID,Krijger Gerard C4,Ramakers Ruud M567,Beekman Freek J567,Dadachova Ekaterina8ORCID,Lam Marnix GEH4,Vogely H Charles2,van der Wal Bart CH2,van Strijp Jos AG1,Horswill Alexander R39,Weinans Harrie210,Rooijakkers Suzan HM1ORCID

Affiliation:

1. Department of Medical Microbiology, University Medical Centre Utrecht

2. Department of Orthopedics, University Medical Centre Utrecht

3. Department of Immunology and Microbiology, University of Colorado School of Medicine

4. Department of Radiology and Nuclear Medicine, University Medical Centre Utrecht

5. MILabs B.V

6. Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center

7. Department of Radiation Science and Technology, Delft University of Technology

8. College of Pharmacy and Nutrition, University of Saskatchewan

9. Department of Veterans Affairs, Eastern Colorado Health Care System

10. Department of Biomechanical engineering, TU Delft

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.

Funder

Health~Holland

National Institutes of Health

QUARAT: Quantitative Universal Radiotracer Tomography

U.S. Department of Veteran Affairs

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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