Staphylococcus aureus infections are a major threat in healthcare, requiring adequate early-stage diagnosis and treatment. This calls for novel diagnostic tools that allow noninvasive in vivo detection of staphylococci. Here we performed a preclinical study to investigate a novel fully-human monoclonal antibody 1D9 that specifically targets the immunodominant staphylococcal antigen A (IsaA). We show that 1D9 binds invariantly to S. aureus cells and may further target other staphylococcal species. Importantly, using a human post-mortem implant model and an in vivo murine skin infection model, preclinical feasibility was demonstrated for 1D9 labeled with the near-infrared fluorophore IRDye800CW to be applied for direct optical imaging of in vivo S. aureus infections. Additionally, 89Zirconium-labeled 1D9 could be used for positron emission tomography imaging of an in vivo S. aureus thigh infection model. Our findings pave the way towards clinical implementation of targeted imaging of staphylococcal infections using the human monoclonal antibody 1D9.

Bacterial infections are a frequently occurring and major complication in human healthcare, in particular due to the rapid increase of antimicrobial resistance and the emergence of pan-drug-resistant microbes. Current anatomical and functional imaging modalities are insufficiently capable of distinguishing sites of bacterial infection from sterile inflammation. Therefore, definitive diagnosis of an infection can often only be obtained by tissue biopsy and subsequent culture and, occasionally, a definite diagnosis even appears to be impossible. To accurately diagnose bacterial infections early, novel imaging modalities are urgently needed. In this regard, bacteria-targeted imaging is an attractive option due to its specificity. Here, different bacteria-targeted imaging approaches are reviewed, and their promising future perspectives are discussed.

Conflict of interest: KPF reports that he is an employee of PerkinElmer Inc., the manufacturer of optical and PET imaging equipment. GMVD is CEO, founder, and shareholder of AxelaRx/ TRACER group and CSO AxelaRx Biosciences Inc. JMVD has filed a patent application on the use of 1D9 (US 9,944,694 B2), which is owned by his employer University Medical Center Groningen.