Simultaneous exposure to intracellular and extracellular photosensitizers for the treatment of Staphylococcus aureus infections.

Staphylococcus aureus is a serious threat to public health due to the rise of antibiotic resistance in this organism, which can prolong or exacerbate skin and soft tissue infections (SSTIs). Methicillin-resistant S. aureus is a Gram-positive bacterium and a leading cause of SSTIs. As such, many efforts are underway to develop therapies that target essential biological processes in S. aureus. Antimicrobial photodynamic therapy is effective alternative to antibiotics, therefore we developed an approach to simultaneously expose S. aureus to intracellular and extracellular photoactivators. A near infrared photosensitizer was conjugated to human monoclonal antibodies (mAbs) that target the S. aureus Isd heme acquisition proteins. Additionally, the compound VU0038882 was developed to increase photoactivatable porphyrins within the cell. Combinatorial PDT treatment of drug-resistant S. aureus exposed to VU0038882 and conjugated anti-Isd mAbs proved to be an effective antibacterial strategy in vitro and in a murine model of SSTIs.