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The Biochemical Mechanisms of Antimicrobial Photodynamic Therapy

Sabino, CP, Ribeiro, MS, Wainwright, M, Dos Anjos, C, Sellera, FP, Dropa, M, Nunes, NB, Brancini, GTP, Braga, GUL, Arana-Chavez, VE, Freitas, RO, Lincopan, N and Baptista, MS (2022) The Biochemical Mechanisms of Antimicrobial Photodynamic Therapy. Photochemistry and photobiology. ISSN 0031-8655

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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.

Item Type: Article
Additional Information: This is the peer reviewed version of the following article: Sabino, C.P., Ribeiro, M.S., Wainwright, M., dos Anjos, C., Sellera, F.P., Dropa, M., Nunes, N.B., Brancini, G.T.P., Braga, G.U.L., Arana-Chavez, V.E., Freitas, R.O., Lincopan, N. and Baptista, M.S. (2022), The Biochemical Mechanisms of Antimicrobial Photodynamic Therapy1. Photochem Photobiol., which has been published in final form at https://doi.org/10.1111/php.13685. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited.
Uncontrolled Keywords: Biophysics; 02 Physical Sciences; 03 Chemical Sciences; 06 Biological Sciences
Subjects: R Medicine > RS Pharmacy and materia medica
Divisions: Pharmacy & Biomolecular Sciences
Publisher: Wiley
SWORD Depositor: A Symplectic
Date Deposited: 05 Sep 2022 14:18
Last Modified: 12 Aug 2023 00:50
DOI or Identification number: 10.1111/php.13685
URI: https://researchonline.ljmu.ac.uk/id/eprint/17474

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