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 under way to develop therapies that target essential biological processes in S. aureus. Antimicrobial photo-dynamic therapy is an effective alternative to antibiotics; therefore we developed an approach to simultaneously expose S. aureus to intracellular and extracellular photo-sensitizers. A near infrared photosensitizer was conjugated to human monoclonal antibodies (MAbs) that target the S. aureus iron-regulated surface determinant (Isd) heme acquisition proteins. In addition, the compound VU0038882 was developed to increase photoactivatable porphyrins within the cell. Combinatorial photodynamic 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.

Automated summary

Staphylococcus aureus poses a serious threat to public health due to antibiotic resistance. Antimicrobial photo-dynamic therapy has been developed as an effective alternative. Combinatorial photodynamic treatment of drug-resistant S. aureus has shown effectiveness in vitro and in a murine model of SSTIs.