Global priority multidrug-resistant pathogens do not resist photodynamic therapy

Author(s)

Sabino, Caetano Padial ^{[1, 2]} ; Wainwright, Mark ^[3] ; Ribeiro, Martha Simoes ^[4] ; Sellera, Fabio Parra ^[5] ; dos Anjos, Carolina ^[5] ; Baptista, Mauricio da Silva ^[6] ; Lincopan, Nilton ^{[7, 1, 8]}

Affiliation

^[1] Univ Sao Paulo, Fac Pharmaceut Sci, Dept Clin Anal, Sao Paulo - Brazil

^[2] Sci & Commercial LTD, BioLambda, Sao Paulo, SP - Brazil

^[3] Liverpool John Moores Univ, Sch Pharm & Biomol Sci, Liverpool, Merseyside - England

^[4] Natl Commiss Nucl Energy, Ctr Lasers & Applicat Nucl & Energy Res Inst, Sao Paulo, SP - Brazil

^[5] Univ Sao Paulo, Sch Vet Med & Anim Sci, Dept Internal Med, Sao Paulo - Brazil

^[6] Univ Sao Paulo, Inst Chem, Dept Biochem, Sao Paulo, SP - Brazil

^[7] Univ Sao Paulo, Inst Biomed Sci, Dept Microbiol, Sao Paulo - Brazil

^[8] Univ Sao Paulo, Inst Biomed Sci, Dept Microbiol, Sao Paulo, Brazil.Sabino, Caetano Padial, Sci & Commercial LTD, BioLambda, Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY; v. 208, JUL 2020.
• Web of Science Citations: 13

Abstract

Microbial drug-resistance demands immediate implementation of novel therapeutic strategies. Antimicrobial photodynamic therapy (aPDT) combines the administration of a photosensitizer (PS) compound with low-irradiance light to induce photochemical reactions that yield reactive oxygen species (ROS). Since ROS react with nearly all biomolecules, aPDT offers a powerful multitarget method to avoid selection of drug-resistant strains. In this study, we assayed photodynamic inactivation under a standardized method, combining methylene blue (MB) as PS and red light, against global priority pathogens. The species tested include Acinetobacter baumannii, Klebsiella aerogenes, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterococcus faecium, Enterococcus faecalis, Staphylococcus aureus, Candida albicans and Cryptococcus neoformans. Our strain collection presents resistance to all tested antimicrobials ( > 50). All drug-resistant strains were compared to their drugsensitive counterparts. Regardless of resistance phenotype, MB-aPDT presented species-specific dose-response kinetics. More than 5log(10) reduction was observed within less than 75 s of illumination for A. baumannii, E. coli, E. faecium, E. faecalis and S. aureus and within less than 7 min for K. aerogenes, K. pneumoniae, P. aeruginosa, C. albicans and C. neoformans. No signs of correlations in between drug-resistance profiles and aPDT sensitivity were observed. Therefore, MB-aPDT can provide effective therapeutic protocols for a very broad spectrum of pathogens. Hence, we believe that this study represents a very important step to bring aPDT closer to implementation into mainstream medical practices. (AU)

• 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: 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: 13/07937-8 - Redoxome - Redox Processes in Biomedicine
• Grantee: Ohara Augusto
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• 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