Aim

Infections represent a serious threat to the successful utilization of implants in modern medicine. Implant-associated infections are difficult to treat, because they involve biofilms that protect bacteria from the immune system and harbour antibiotic-tolerant persister cells.

In this work, we developed an antibody-drug conjugate (ADC) containing the anti-neoplastic drug mitomycin C (MMC) as a novel treatment paradigm for implant-associated infections. MMC was chosen as it is a potent antimicrobial against biofilms and its synthesis into an ADC was chosen to alleviate toxicity. Following development and synthesis of the ADC, stability and release of MMC was measured. We then used the ADC to kill bacteria in suspension and in biofilms, in vitro and in vivo.

Aim

Implant infections caused by Staphylococcus aureus are difficult to treat due to biofilm formation, which complicates surgical and antibiotic treatment. Herewith we introduce an alternative approach using monoclonal antibodies (mAbs) targeting S. aureus and provide the biodistribution and specificity in a mouse implant infection model.

Aim

“Implant associated Staphylococcus aureus or S. epidermidis infections are often difficult to treat due to the formation of biofilms on prosthetic material. Biofilms are bacterial communities adhered to a surface with a self-made extracellular polymeric substance that surrounds resident bacteria. In contrast to planktonic bacteria, bacteria in a biofilm are in an adherent, dormant state and are insensitive to most antibiotics. In addition, bacteria in a biofilm are protected from phagocytic cells of the immune system. Therefore, complete surgical removal and replacement of the prosthetic implant is often necessary to treat this type of infections. Neutrophils play a crucial role in clearing bacterial pathogens. They recognize planktonic bacteria via immunoglobulin (Ig) and complement opsonisation. In this project, we aim to evaluate the role of IgG and complement in the recognition and clearance of staphylococcal biofilms by human neutrophils. Furthermore, we evaluate if monoclonal antibodies (mAbs) targeting biofilm structures can enhance recognition and clearance of staphylococcal biofilms by the human immune system.”