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Global priority multidrug-resistant pathogens do not resist photodynamic therapy.

Caetano Padial Sabino1, Mark Wainwright2, Martha Simões Ribeiro3

  • 1BioLambda, Scientific and Commercial LTD, São Paulo, SP, Brazil.; Department of Clinical Analysis, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil..

Journal of Photochemistry and Photobiology. B, Biology
|May 24, 2020
PubMed
Summary

Antimicrobial photodynamic therapy (aPDT) using methylene blue effectively inactivates drug-resistant pathogens. This approach offers a broad-spectrum treatment strategy, paving the way for clinical implementation.

Keywords:
Drug resistanceESKAPEMultidrug resistancePhotoinactivation

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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.