Drug-resistant clinical Candida responded to 5-aminolevulinic acid photodynamic therapy (ALA-PDT) in vitro via

Zhiya Yang1, Yonghong Zhang2,3, Dongmei Li4

  • 1The Laboratory of Medical Mycology, Jining No. 1 People's Hospital, Jining, Shandong, China.

Insights

Photodynamic therapy using 5-aminolevulinic acid (ALA-PDT) effectively combats drug-resistant Candida infections by increasing reactive oxygen species and inhibiting fungal growth. This approach shows promise for treating difficult candidiasis cases.

Area of Science:

  • Mycology
  • Photomedicine
  • Antimicrobial Resistance

Background:

  • Drug-resistant fungal infections, particularly candidiasis, pose a significant global health challenge.
  • Traditional antifungal therapies face limitations due to emerging resistance in Candida species.
  • 5-aminolevulinic acid photodynamic therapy (ALA-PDT) is explored as an alternative treatment strategy.

Purpose of the Study:

  • To evaluate the therapeutic efficacy of ALA-PDT against drug-resistant Candida strains.
  • To elucidate the mechanisms underlying ALA-PDT's antifungal activity.
  • To assess ALA-PDT's impact on gene expression, cell morphology, and reactive oxygen species generation.

Main Methods:

  • Isolation and identification of drug-resistant Candida strains from patient samples.
  • Antifungal susceptibility testing against azoles, micafungin, amphotericin B, and terbinafine.
  • In vitro treatment with ALA-PDT, followed by assessment of fungal killing, ROS levels, and biofilm formation.
  • Scanning electron microscopy (SEM) for cell-wall morphology analysis.
  • RNA sequencing (RNA-seq) to evaluate gene expression related to fungal growth and morphology.

Main Results:

  • ALA-PDT demonstrated effective eradication of azole-resistant Candida albicans in vitro.
  • Significant increases in intracellular reactive oxygen species (ROS) levels were observed post-ALA-PDT treatment.
  • SEM revealed cell-wall disruption, and RNA-seq indicated downregulation of mycelia-related genes.
  • Candida albicans and Candida tropicalis were predominant species, often isolated from male ICU patients over 40.

Conclusions:

  • ALA-PDT effectively inhibits the growth of drug-resistant Candida species through ROS-mediated cell damage and suppression of mycelial gene expression.
  • ALA-PDT presents a promising therapeutic option for refractory candidiasis.
  • The study provides mechanistic insights into the antifungal action of ALA-PDT, supporting its clinical potential.