Light-based antifungal strategy: an approach to control disseminated Candida auris infection

• Grant number: 21/14119-6
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): August 01, 2022
• Effective date (End): May 31, 2026
• Field of knowledge: Biological Sciences - Biophysics - Radiology and Photobiology
• Principal Investigator: Martha Simões Ribeiro
• Grantee: Abdênego Rodrigues da Silva
• Host Institution: Instituto de Pesquisas Energéticas e Nucleares (IPEN). Secretaria de Desenvolvimento Econômico (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

The increasing global increase in fungal resistance to conventional drugs requires new therapeutic cost-effective approaches. Photodynamic therapy (PDT) appears in this scenario as a non-invasive treatment option, which has shown good results in the eradication of bacteria, fungi, and parasites, with the advantage of not selecting resistant microorganisms. PDT involves the use of a photosensitizer (PS), light, and oxygen. Cell death occurs when PS absorbs light, triggering the production of reactive oxygen species, inactivating microbial cells by oxidative stress. In this project, we will develop a model of disseminated infection by Candida auris, which is an emerging fungus highly resistant to conventional antifungal agents, in mice. The animals will be immunosuppressed and, after confirmation of immunosuppression, we will induce disseminated infection by inoculating C. auris by gavage. After establishing the model, the animals will be submitted to PDT mediated by 2 different PSs: methylene blue (MB) and zinc porphyrin (ZnHexP). The PSs will be administered through the tail vein and after 24 h, they will receive whole-body irradiation with red and blue light, respectively. Animals will be clinically monitored until euthanasia. Blood, urine, feces, liver, and kidney samples will be collected to quantify the fungal load. (AU)