Antimicrobial photodynamic therapy: an effective alternative approach to control fungal infections

Abstract

Skin mycoses are caused mainly by dermatophytes, which are fungal species that primarily infect areas rich in keratin such as hair, nails, and skin. Significantly, there are increasing rates of antimicrobial resistance among dermatophytes, especially for Trichophyton rubrum, the most frequent etiologic agent worldwide. Hence, investigators have been developing new therapeutic approaches, including photodynamic treatment. Photodynamic therapy (PDT) utilizes a photosensitive substance activated by a light source of a specific wavelength. The photoactivation induces cascades of photochemicals and photobiological events that cause irreversible changes in the exposed cells. Although photodynamic approaches are well established experimentally for the treatment of certain cutaneous infections, there is limited information about its mechanism of action for specific pathogens as well as the risks to healthy tissues. In this work, we have conducted a comprehensive review of the current knowledge of PDT as it specifically applies to fungal diseases. The data to date suggests that photodynamic treatment approaches hold great promise for combating certain fungal pathogens, particularly dermatophytes.

Keywords: fungal cells; light source; photochemicals and photobiological events; photodynamic inhibition; photosensitizer; treatment.

FIGURE 1

Simplified schematic representation of a Jablonski diagram. The photosensitizer (PS) at the ground state (S₀) transitions after irradiation by a light source to its first single activate state (S₁). To return to its ground state, the PS emits energy by fluorescence or phosphorescence (after reaching the triplet state – T₁).

FIGURE 2

Schematic illustration of the aPI (TBO + LED 630 nm) effects on fungal cell. In this illustration with Trichophyton rubrum conidia, toluidine blue O (TBO) and LED light were used as example according to present the mechanism described by Baltazar Lde et al. (2013). Activation of TBO (both intra and extracellular) increases l-arginine levels, the substrate of oxide nitric synthase (NOS), which results in increasing NO^∙ levels. The increased availability of free electrons increases H₂O₂ production. Moreover, NO^∙ can react with O₂^-, generating ONOO^∙. In eukaryotic cells generation of NO^∙ occurs by oxidation of l-arginine. All these toxic radicals can react with the cell membrane and cytosolic components, leading to cell damage.