Highly Potent Photoinactivation of Bacteria Using a Water-Soluble, Cell-Permeable, DNA-Binding Photosensitizer

• DOI: 10.1021/acsinfecdis.1c00313
• Publication Date: 2021-10-07T11:41:41Z
• Authors: Elyse M. Digby; Tianyi Ma; Warren R. Zipfel; Joshua N. Milstein; Andrew A. Beharry
• Keywords: Staphylococcus aureus; 0303 health sciences; 03 medical and health sciences; Photosensitizing Agents; Bacteria; Light; Escherichia coli; Animals; Water; DNA; 3. Good health

Antimicrobial photodynamic therapy (APDT) employs a photosensitizer, light, and molecular oxygen to treat infectious diseases via oxidative damage, with low likelihood for the development of resistance. For optimal APDT efficacy, photosensitizers cationic charges that can permeate bacteria cells bind intracellular targets are desired not limit damage outer bacterial structure. Here we report application brominated DAPI (Br-DAPI), water-soluble, DNA-binding photosensitizer eradication both Gram-negative Gram-positive (as demonstrated on N99 Escherichia coli Bacillus subtilis, respectively). We observe uptake Br-DAPI, ROS-mediated cell death one- two-photon excitation, selective photocytotoxicity over mammalian cells. Photocytotoxicity E. B. subtilis occurred at submicromolar concentrations (IC50 = 0.2–0.4 μM) light doses (5 min irradiation times, 4.5 J cm–2 dose), making it superior commonly employed phenothiazinium such as methylene blue. Given its high potency excitability, Br-DAPI is promising novel in vivo applications.