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Rose Bengal-Mediated Photodynamic Therapy to Inhibit Candida albicans
Published on: March 24, 2022
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.
Abstract:
Photodynamic therapy (PDT) has emerged as a potential strategy to combat drug-resistant fungal infections. This study aimed to evaluate the therapeutic efficacy of 5-aminolevulinic acid PDT (ALA-PDT) against drug-resistant Candida strains isolated from patients with candidiasis and to elucidate its underlying mechanisms. Drug-resistant strains were identified by their reduced antifungal susceptibility to azoles, micafungin, amphotericin B, and terbinafine. RNA sequencing (RNA-seq) was used to assess gene expression related to mycelial formation and fungal growth. Scanning electron microscopy (SEM) was employed to observe cell-wall morphology after ALA-PDT treatment. Biofilm formation and intracellular reactive oxygen species (ROS) levels were also measured to investigate the mechanism of ALA-PDT-mediated fungal killing. Candida albicans and Candida tropicalis accounted for over half, predominantly from male ICU patients aged over 40 years. Candida spp. strains exhibited resistance rates of approximately 69.38% to terbinafine, 40.8% to azole antifungals, and 16.3% to micafungin among 49 drug-resistant isolates. Treatment with 20% ALA-PDT effectively eradicated those azole-resistant C. albicans in vitro, increased fungal killing, and significantly increased intracellular ROS levels. SEM analysis revealed varying degrees of cell-wall disruption, and RNA-seq demonstrated downregulation of mycelia-related genes following ALA-PDT. ALA-PDT effectively inhibits drug-resistant Candida spp. growth by inducing ROS-mediated cell damage and suppressing mycelial gene expression. These findings highlight ALA-PDT as a promising therapeutic approach for refractory candidiasis and provide mechanistic insights into its antifungal activity.
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.

