A genome-wide screen for tolerance to rose bengal photodynamic therapy and its use in onychomycosis treatment

J. Houang, G. G. Perrone, C. Pedrinazzi, L. Longo, D. Mawad, P. C. Boughton, A. J. Ruys, A. Lauto

Research output: Chapter in Book / Conference PaperConference Paperpeer-review

1 Citation (Scopus)

Abstract

![CDATA[The clinical use of photodynamic therapy (PDT) with rose bengal (RB) is emerging as an effective treatment for a range of applications given its non-invasive and localised mode of delivery. In particular, rose bengal PDT has shown promising antifungal action in vitro. While focus has largely been on the physical and chemical impacts of PDT on the cell, an understanding of the role of genetics underpinning the cellular response is still limited. We have, therefore, reported a screen of the entire non-essential gene library of the model organism, Saccharomyces cerevisiae, using rose bengal PDT to ascertain the key genetic pathways affecting fungal tolerance to PDT. We also investigated the dosage of PDT required to eradicate Trichophyton rubrum spores, the main causative organism of onychomycosis infection. Following this, we conducted a pilot patient study of six patients (seven toenails) for the treatment of onychomycosis using rose bengal PDT (140 μM RB and ∼763 J/cm2 green light), where the clinical treatment protocol was developed on the basis of the in vitro outcomes. The key biochemical pathways identified by the genetic screen as having altered tolerance to PDT included ergosterol biosynthesis, vacuolar acidification, and purine/S-adenosyl-L-methionine biosynthesis. The subsequent pilot patient study saw the complete cure of onychomycosis for all patients within three to five treatment sessions in the absence of pain or other local side effects. The outcome of the genetic screen for tolerance may thus inform the development of efficient clinical treatments using rose bengal PDT.]]
Original languageEnglish
Title of host publicationProceedings of SPIE BIOS: Photonic Diagnosis and Treatment of Infections and Inflammatory Diseases II (Volume 10863), 4-5 February 2019, San Francisco, California, United States
PublisherSPIE
Pages108630N-1-108630N-16
Number of pages16
ISBN (Print)9781510623682
DOIs
Publication statusPublished - 2019
EventSPIE BIOS: Photonic Diagnosis and Treatment of Infections and Inflammatory Diseases -
Duration: 4 Feb 2019 → …

Publication series

Name
ISSN (Print)1605-7422

Conference

ConferenceSPIE BIOS: Photonic Diagnosis and Treatment of Infections and Inflammatory Diseases
Period4/02/19 → …

Keywords

  • Saccharomyces cerevisiae
  • biochemistry
  • biosynthesis
  • genes
  • onychomycosis
  • rose bengal
  • yeast

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