The Biochemical Mechanisms of Antimicrobial Photodynamic Therapy(1)

Author(s):Show less -

Sabino, Caetano P. ; Ribeiro, Martha S. ; Wainwright, Mark ; Dos Anjos, Carolina ; Sellera, Fabio P. ; Dropa, Milena ; Nunes, Nathalia B. ; Brancini, Guilherme T. P. ; Braga, Gilberto U. L. ; Arana-Chavez, Victor E. ; Freitas, Raul O. ; Lincopan, Nilton ; Baptista, Mauricio S.

• Document type: Journal article
• Source: Photochemistry and Photobiology; v. N/A, p. 9-pg., 2022-08-12.

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. (AU)

• FAPESP's process: 16/25095-2 - BACTERIAL PHOTOINACTIVATION OF MASTITIS PATHOGENS BY BLUE LIGHT: MECHANISMS OF ACTION AND CELL SECURITY - PRE-CLINICAL STUDY
• Grantee: Carolina dos Anjos
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 17/22406-0 - Development of a smart clinical equipment for phototherapies with automatic dosimetry calibration and on demand payment
• Grantee: Caetano Padial Sabino
• Support Opportunities: Research Grants - Innovative Research in Small Business - PIPE
• FAPESP's process: 16/08593-9 - Pan-Resistome of beta-lactamase (KPC-2, CTX-M-8, CTX-M-15)-producing Klebsiella pneumoniae and Escherichia coli isolates endemic in Brazil
• Grantee: Nilton Erbet Lincopan Huenuman
• Support Opportunities: Regular Research Grants
• FAPESP's process: 13/07937-8 - Redoxome - Redox Processes in Biomedicine
• Grantee: Ohara Augusto
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 19/10851-4 - SYNERGISTIC ACTIVITY OF BLUE LIGHT IN COMBINATION WITH CHEMOTHERAPEUTIC ANTIMICROBIAL AGAINST DRUG-RESISTANT PATHOGENS
• Grantee: Carolina dos Anjos
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate