Global priority multidrug-resistant pathogens do not resist photodynamic therapy

Area of Science:

• Microbiology
• Photochemistry
• Drug Discovery

Background:

• Microbial drug resistance necessitates novel therapeutic strategies.
• Antimicrobial photodynamic therapy (aPDT) utilizes photosensitizers and light to generate reactive oxygen species (ROS), offering a multitarget approach against resistant strains.
• ROS's broad reactivity minimizes the selection of resistant microbial populations.

Purpose of the Study:

• To evaluate the efficacy of methylene blue-based aPDT against a panel of multidrug-resistant priority pathogens.
• To compare the aPDT sensitivity of drug-resistant strains with their drug-sensitive counterparts.
• To assess the potential of MB-aPDT as a viable therapeutic option for a wide range of infections.

Main Methods:

• A standardized photodynamic inactivation method was employed using methylene blue (MB) as the photosensitizer (PS) and red light.
• The study tested MB-aPDT against clinically relevant pathogens including Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus, and Candida albicans, among others.
• Both drug-resistant and drug-sensitive strains were assayed to determine the impact of resistance phenotypes on aPDT efficacy.

Main Results:

• MB-aPDT demonstrated species-specific dose-response kinetics against all tested pathogens, irrespective of their resistance profiles.
• Rapid inactivation ( >5log₁₀ reduction) was achieved within 75 seconds for A. baumannii, E. coli, E. faecium, E. faecalis, and S. aureus.
• Slower inactivation kinetics (within 7 minutes) were observed for K. aerogenes, K. pneumoniae, P. aeruginosa, C. albicans, and C. neoformans.
• No correlation was found between existing antimicrobial resistance profiles and sensitivity to MB-aPDT.

Conclusions:

• Methylene blue-based aPDT is a highly effective antimicrobial strategy against a broad spectrum of priority pathogens, including multidrug-resistant strains.
• The efficacy of MB-aPDT is independent of the pathogen's resistance to conventional antibiotics.
• This study provides strong evidence supporting the advancement of aPDT towards clinical application in combating microbial infections.