Abstract

Fungal infections are increasing in prevalence worldwide. The paucity of available antifungal drug classes, combined with the increased occurrence of multidrug resistance in fungi, has led to new clinical challenges in the treatment of fungal infections. Candida auris is a recently emerged multidrug resistant human fungal pathogen that has become a worldwide public health threat. C. auris clinical isolates are often resistant to one or more antifungal drug classes, and thus, there is a high unmet medical need for the development of new therapeutic strategies effective against C. auris. Additionally, C. auris possesses several virulence traits, including the ability to form biofilms, further contributing to its drug resistance, and complicating the treatment of C. auris infections. Here we assessed red, green, and blue visible lights alone and in combination with photosensitizing compounds for their efficacies against C. auris biofilms. We found that (1) blue light inhibited and disrupted C. auris biofilms on its own and that the addition of photosensitizing compounds improved its antibiofilm potential; (2) red light inhibited and disrupted C. auris biofilms, but only in combination with photosensitizing compounds; and (3) green light inhibited C. auris biofilms in combination with photosensitizing compounds, but had no effects on disrupting C. auris biofilms. Taken together, our findings suggest that photodynamic therapy could be an effective non-drug therapeutic strategy against multidrug resistant C. auris biofilm infections.

Highlights

  • Fungi are responsible for a wide range of infections in humans, including superficial skin infections as well as life-threatening disseminated infections (Brown et al, 2012)

  • We found that red and green visible lights on their own had no effects on C. auris biofilms in any of the three biofilm assays compared to the untreated control (Figures 2A, B)

  • We found that blue light on its own had no effect at inhibiting C. auris biofilm formation in the adherence inhibition biofilm assay compared to the untreated control (Figure 2C)

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Summary

Introduction

Fungi are responsible for a wide range of infections in humans, including superficial skin infections as well as life-threatening disseminated infections (Brown et al, 2012). Three major classes of antifungal drugs (the polyenes, azoles, and echinocandins) are the most commonly used therapeutic agents for treating invasive fungal infections in humans (Odds et al, 2003; Prasad et al, 2016). C. auris is typically isolated from the skin, nares, wounds, axilla, and urinary tracts, as well as the bloodstream, bones, and cerebrospinal fluids of patients with severe invasive infections (Borman et al, 2016; Calvo et al, 2016; Morales-López et al, 2017; Horton and Nett, 2020). Once C. auris infections become systemic, they are associated with high mortality rates, ranging from 30-72%, with the highest mortality rates reported in patients with histories of extended hospital stays, implanted medical devices, or patients who have previously been treated with antifungal drugs (Cortegiani et al, 2018; Osei Sekyere, 2018; Spivak and Hanson, 2018; Chakrabarti and Singh, 2020; Garcia-Bustos et al, 2020; Shastri et al, 2020)

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