The Biochemical Mechanisms of Antimicrobial Photodynamic Therapy †
Caetano P. Sabinoa b✉, Martha Simões Ribeiroc✉, MARK S. WAINWRIGHTd e, Carolina dos Anjosf g h i, Fábio P. Selleraf j, Milena Dropak, Nathalia B. Nunesl, Guilherme Thomaz Pereira Brancinil, Gilberto Úbida Leite Bragal, Victor Elias Arana-Chavezm, Raul O. Freitasn o, Nilton Lincopánb p, Maurı́cio S. Baptistaq✉
- aBioLambda, Scientific and Commercial Ltd. São Paulo SP Brazil
- bDepartment of Clinical and Toxicological Analysis School of Pharmaceutical Sciences, University of São Paulo São Paulo SP Brazil
- cCenter for Lasers and Applications Energy and Nuclear Research Institute São Paulo SP Brazil
- dSchool of Pharmacy &
- eBiomolecular Sciences Liverpool John Moores University Liverpool UK
- fDepartment of Internal Medicine School of Veterinary Medicine and Animal Science, University of São Paulo São Paulo SP Brazil
- gVaccine and Immunotherapy Center Massachusetts General Hospital, Harvard Medical School Boston MA USA
- hWellman Center for Photomedicine Massachusetts General Hospital, Harvard Medical School Boston MA USA
- iVaccine and Immunotherapy Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
- jSchool of Veterinary Medicine Metropolitan University of Santos Santos SP Brazil
Papers open inside SciRah from the original publisher or repository; SciRah never hosts them.
Abstract
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.
TL;DRA deeper mechanistic understanding of aPDT is provided that can guide the scientific community toward the development of optimized photosensitizing drugs and also rationally propose synergistic combinations with antimicrobial chemotherapy. (Semantic Scholar)