Photodynamic fungicidal efficacy of hypericin and dimethyl methylene blue against azole‐resistant Candida albicans strains

Abstract

Antimicrobial photodynamic therapy (aPDT) is an emerging alternative to treat infections based on the use of photosensitisers (PSs) and visible light. To investigate the fungicidal effect of PDT against azole-resistant Candida albicans strains using two PSs with a different mechanism of action, hypericin (HYP) and 1,9-dimethyl methylene blue (DMMB), comparing their efficacy and the reactive oxygen species (ROS) species involved in their cytotoxicity. Azole-resistant and the azole-susceptible C. albicans strains were used. Solutions of 0.5 and 4 McFarland inoculum of each Candida strain were treated with different concentrations of each PS, and exposed to two light-emitting diode light fluences (18 and 37 J cm⁻²). Mechanistic insight was gained using several ROS quenchers. The minimal fungicidal concentration of HYP for ≥3 log₁₀ CFU reduction (0.5 McFarland) was 0.62 μmol l⁻¹ for most strains, whereas for DMMB it ranged between 1.25 and 2.5 μmol l⁻¹. Increasing the fluence to 37 J cm⁻² allowed to reduce the DMMB concentration. Higher concentrations of both PSs were required to reach a 6 log₁₀ reduction (4 McFarland). H₂O₂ was the main phototoxic species involved in the fungicidal effect of HYP-aPDT whereas ¹O₂ was more important for DMMB-based treatments. aPDT with either HYP or DMMB is effective in killing of C. albicans strains independent of their azole resistance pattern. HYP was more efficient at low fungal concentration and DMMB at higher concentrations.

On the mechanism of Candida tropicalis biofilm reduction by the combined action of naturally-occurring anthraquinones and blue light

“…Insight on the photo-induced biofilm reduction mechanism was gained by studying the effect of the ROS quenchers Tiron (for O 2 •− ) and sodium azide (for 1 O 2 ) on a 48h-biofilm [31,32]. AQs (56 μM) and quenchers (500 mM) were added to biofilms at the same time, and the assay was performed in the dark and under irradiation using the conditions mentioned above.…”

Effectiveness of the Photoactive Dye Methylene Blue versus Caspofungin on the Candida parapsilosis Biofilm in vitro and ex vivo

“…Photodynamic inactivation (PDI) is a promising antimicrobial modality using a nontoxic photoactive dye for the inactivation of various pathogenic microorganisms. When such a compound is sensitized by light of a particular wavelength, reactive oxygen species capable of killing microorganisms are formed in the presence of oxygen . The possibilities of using PDI to promote microbial eradication are being considered more and more .…”

Photodynamic Therapy: Current Status and Future Directions

“…It was clinically approved more than a quarter of a century ago for the treatment of a small number of selected tumors [1] and has expanded tremendously to include areas of application as diverse as cardiology [2,3], urology [4], immunology [5], ophthalmology [6,7], dentistry [8,9], dermatology [10,11] and cosmetics [12,13]. Antimicrobial/antiviral PDT has been successfully used for the treatment of viral infections [14,15], against antibiotic-resistant bacterial [16,17] and fungal strains [18,19,20], for the inactivation of pathogens in blood products [21], for water sterilization [22,23] and for disinfection and sanitation of surfaces [24,25]. The photodynamic process is successfully used for drug delivery and the release of endocytosed macromolecules in the cytosol [26,27].…”