New Insights in Phenothiazinium-Mediated Photodynamic Inactivation of Candida Auris

Abdênego R Silva1, Fernanda V Cabral1, Camila R Silva1

  • 1Center for Lasers and Applications, Nuclear and Energy Research Institute (IPEN-CNEN), São Paulo 05508-000, SP, Brazil.

Insights

Photodynamic inactivation using 1,9-dimethyl methylene blue (DMMB-PDI) effectively eradicated Candida auris yeasts and biofilms. This novel approach shows promise for combating this hazardous, drug-resistant hospital-acquired pathogen.

Area of Science:

  • Antimicrobial photodynamic therapy
  • Emerging infectious diseases
  • Medical mycology

Background:

  • Candida auris is a hazardous hospital-acquired pathogen known for its antifungal resistance.
  • Effective management strategies for Candida auris infections are urgently needed.
  • Photodynamic inactivation (PDI) offers a potential alternative therapeutic approach.

Purpose of the Study:

  • To evaluate the efficacy of photodynamic inactivation using methylene blue (MB-PDI) or 1,9-dimethyl MB (DMMB-PDI) against Candida auris.
  • To compare the mechanisms of action between MB-PDI and DMMB-PDI.
  • To assess the effectiveness of DMMB-PDI against Candida auris biofilms and its cytotoxicity.

Main Methods:

  • Quantification of colony-forming units and reactive oxygen species (ROS) production.
  • Assessment of lipid peroxidation (LPO) and mitochondrial membrane potential (ΔΨm).
  • Biofilm analysis using metabolic activity, biomass, scanning electron microscopy, and optical coherence tomography; cytotoxicity assays in mammalian cells.

Main Results:

  • DMMB-PDI eradicated Candida auris yeasts at 3 μM, irrespective of light dose, while MB-PDI required higher concentrations and light doses.
  • DMMB-PDI induced significantly higher ROS, LPO, and ΔΨm compared to MB-PDI.
  • DMMB-PDI inhibited biofilm formation, eradicated mature biofilms, and demonstrated no cytotoxicity in fibroblasts.

Conclusions:

  • 1,9-dimethyl MB-mediated photodynamic inactivation (DMMB-PDI) is a highly effective strategy against Candida auris yeasts and biofilms.
  • DMMB-PDI exhibits a superior mechanism of action involving increased ROS production, LPO, and mitochondrial disruption.
  • DMMB-PDI presents a promising, non-toxic therapeutic candidate to address the global threat of Candida auris infections.