5-Aminolevulinic acid-mediated photodynamic therapy has effective antifungal activity against Sporothrix globosa in vitro

Mycoses. 2020 Dec;63(12):1311-1320. doi: 10.1111/myc.13171. Epub 2020 Sep 12.

Abstract

Background: An alternative therapy for sporotrichosis is necessary to reduce the treatment time and raise clinical efficacy. The 5-Aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) is a promising platform with which to treat mycoses. However, despite the worldwide prevalence of Sporothrix globosa, a causative agent of sporotrichosis, the effect of ALA-PDT on this pathogen has not been validated.

Objectives: The aim of this study was to evaluate the effect of ALA-PDT on S globosa and the protection of melanin through an in vitro study. The mechanisms involved were also investigated.

Methods: To estimate the survival rate of S globosa treated with ALA-PDT and the protection offered by melanin, the conidia and yeast cells of wild-type S globosa (Mel+), other clinical strains, tricyclazole-treated Mel+ and an albino mutant strain (Mel-) were incubated with and without ALA or irradiation. Reactive oxygen species generation by Mel+ conidia induced by ALA-PDT was assayed. SEM and TEM were conducted to obverse ultrastructural changes in the conidia. A comet assay was performed to evaluate DNA damage.

Results: The survival rate of S globosa conidia and yeast cells significantly decreased following incubation with 1.19M ALA and 162 J/cm2 irradiation in vitro. Melanin was not only capable of protecting the conidia against ALA-PDT, but also against ALA or irradiation alone. After induction by ALA-PDT, alterations in reactive oxygen species generation, DNA damage and ultrastructural changes were observed.

Conclusions: ALA-PDT inhibits the survival of S globosa conidia in vitro and therefore has potential for the treatment of sporotrichosis.

Keywords: Sporothrix globosa; 5-aminolevulinic acid; melanin; photodynamic therapy; reactive oxygen species; sporotrichosis.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aminolevulinic Acid / pharmacology*
  • Antifungal Agents / pharmacology*
  • Female
  • Humans
  • Male
  • Microbial Sensitivity Tests
  • Middle Aged
  • Photochemotherapy*
  • Skin / microbiology
  • Skin / pathology
  • Spores, Fungal / drug effects
  • Sporothrix / drug effects*
  • Sporothrix / isolation & purification
  • Sporothrix / pathogenicity
  • Sporotrichosis / drug therapy
  • Sporotrichosis / microbiology

Substances

  • Antifungal Agents
  • Aminolevulinic Acid

Supplementary concepts

  • Sporothrix globosa