Simultaneous Exposure to Intracellular and Extracellular Photosensitizers for the Treatment of Staphylococcus aureus Infections.
Sydney L DruryAnderson R MillerClare L LautAlec B WalterMonique R BennettMeng SuMingfeng BaiBingwen JingScott B JosephEdward J MetzgerCharles E BaneChad C BlackMary T MacdonaldBrendan F DutterIan M RomaineAlex G WatersonGary A SulikowskiE Duco JansenJames E CroweRichard J SciottiEric P SkaarPublished in: Antimicrobial agents and chemotherapy (2021)
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 in vitro and in a murine model of SSTIs.
Keyphrases
- photodynamic therapy
- staphylococcus aureus
- drug resistant
- public health
- fluorescence imaging
- soft tissue
- multidrug resistant
- biofilm formation
- endothelial cells
- single cell
- gram negative
- reactive oxygen species
- escherichia coli
- transcription factor
- bone marrow
- combination therapy
- drug delivery
- cancer therapy
- candida albicans
- replacement therapy
- smoking cessation