Journal
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
Volume 65, Issue 12, Pages -Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/AAC.00919-21
Keywords
Staphylococcus aureus; antibodies; antimicrobial photodynamic therapy; iron-regulated surface determinant system; photosensitizer; small molecules
Categories
Funding
- Department of Defense [W81XWH-17-2-0003]
- NIH [R0169233, T32GM065086]
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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.
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.
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