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Drury SL, Miller AR, Laut CL, Walter AB, Bennett MR, Su M, Bai M, Jing B, Joseph SB, Metzger EJ, Bane CE, Black CC, Macdonald MT, Dutter BF, Romaine IM, Waterson AG, Sulikowski GA, Jansen ED, Crowe JE, Sciotti RJ, Skaar EP. Simultaneous Exposure to Intracellular and Extracellular Photosensitizers for the Treatment of Staphylococcus aureus Infections. Antimicrobial agents and chemotherapy. 2021 Nov 17;65(65). e0091921.
Abstract
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 photodynamic therapy is an effective alternative to antibiotics; therefore we developed an approach to simultaneously expose S. aureus to intracellular and extracellular photosensitizers. 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 and in a murine model of SSTIs.