The Biochemical Mechanisms of Antimicrobial Photodynamic Therapy † .

Autor: Sabino CP; BioLambda, Scientific and Commercial Ltd., São Paulo, SP, Brazil.; Department of Clinical and Toxicological Analysis, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, SP, Brazil., Ribeiro MS; Center for Lasers and Applications, Energy and Nuclear Research Institute, São Paulo, SP, Brazil., Wainwright M; School of Pharmacy & Biomolecular Sciences, Liverpool John Moores University, Liverpool, UK., Dos Anjos C; Department of Internal Medicine, School of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, SP, Brazil.; Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.; Vaccine and Immunotherapy Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA., Sellera FP; Department of Internal Medicine, School of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, SP, Brazil.; School of Veterinary Medicine, Metropolitan University of Santos, Santos, SP, Brazil., Dropa M; Public Health Laboratory, School of Public Health, University of São Paulo, São Paulo, Brazil., Nunes NB; School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil., Brancini GTP; School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil., Braga GUL; School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil., Arana-Chavez VE; Department of Biomaterials and Oral Biology, University of São Paulo, São Paulo, SP, Brazil., Freitas RO; Brazilian Synchrotron Light Laboratory, Brazilian Center for Research in Energy and Materials, Campinas, SP, Brazil., Lincopan N; Department of Clinical and Toxicological Analysis, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, SP, Brazil.; Department of Microbiology, Institute for Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil., Baptista MS; Department of Biochemistry, Institute of Chemistry, University of São Paulo, São Paulo, SP, Brazil.
Jazyk: angličtina
Zdroj: Photochemistry and photobiology [Photochem Photobiol] 2023 Mar; Vol. 99 (2), pp. 742-750. Date of Electronic Publication: 2022 Aug 12.
DOI: 10.1111/php.13685
Abstrakt: The unbridled dissemination of multidrug-resistant pathogens is a major threat to global health and urgently demands novel therapeutic alternatives. Antimicrobial photodynamic therapy (aPDT) has been developed as a promising approach to treat localized infections regardless of drug resistance profile or taxonomy. Even though this technique has been known for more than a century, discussions and speculations regarding the biochemical mechanisms of microbial inactivation have never reached a consensus on what is the primary cause of cell death. Since photochemically generated oxidants promote ubiquitous reactions with various biomolecules, researchers simply assumed that all cellular structures are equally damaged. In this study, biochemical, molecular, biological and advanced microscopy techniques were employed to investigate whether protein, membrane or DNA damage correlates better with dose-dependent microbial inactivation kinetics. We showed that although mild membrane permeabilization and late DNA damage occur, no correlation with inactivation kinetics was found. On the other hand, protein degradation was analyzed by three different methods and showed a dose-dependent trend that matches microbial inactivation kinetics. Our results provide a deeper mechanistic understanding of aPDT that can guide the scientific community toward the development of optimized photosensitizing drugs and also rationally propose synergistic combinations with antimicrobial chemotherapy.
(© 2022 American Society for Photobiology.)
Databáze: MEDLINE
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