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Antibacterial Photodynamic Inactivation of Antibiotic-Resistant Bacteria and Biofilms with Nanomolar Photosensitizer Concentrations

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    Antibacterial Photodynamic Inactivation of Antibiotic-Resistant Bacteria and Biofilms with Nanomolar Photosensitizer Concentrations
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    ACS Infectious Diseases

    Cite this: ACS Infect. Dis. 2020, 6, 6, 1517–1526
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    https://doi.org/10.1021/acsinfecdis.9b00379
    Published January 8, 2020
    Copyright © 2020 American Chemical Society
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    Abstract

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    Gram-negative bacteria and bacteria in biofilms are very difficult to eradicate and are the most antibiotic-resistant bacteria. Therapeutic alternatives less susceptible to mechanisms of resistance are urgently needed to respond to an alarming increase of resistant nosocomial infections. Antibacterial photodynamic inactivation (PDI) generates oxidative stress that triggers multiple cell death mechanisms that are more difficult to counteract by bacteria. We explore PDI of multidrug-resistant bacterial strains collected from patients and show how positive charge distribution in the photosensitizer drug impacts the efficacy of inactivation. We demonstrate the relevance of size for drug diffusion in biofilms. The designed meso-imidazolyl porphyrins of small size with positive charges surrounding the macrocycle enabled the inactivation of bacteria in biofilms by 6.9 log units at 5 nM photosensitizer concentration and 5 J cm–2, which offers new opportunities to treat biofilm infections.

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    • Detailed experimental procedures and characterization of all compounds (NRM, UV–vis, and mass spectra); analytical procedures; supplementary computational data (PDF)

    • Confocal microscopy of S. aureus biofilms along a 60 min incubation time with 1 μM IP-4-Zn+ (MPG)

    • Confocal microscopy of S. aureus biofilms along a 30 min incubation time with 1 μM IP-2-Zn+ (MPG)

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    Cite this: ACS Infect. Dis. 2020, 6, 6, 1517–1526
    Click to copy citationCitation copied!
    https://doi.org/10.1021/acsinfecdis.9b00379
    Published January 8, 2020
    Copyright © 2020 American Chemical Society
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