Elucidating biological targets of oxidized silver in fungal pathogens****

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Fungi are highly resilient microbiological eukaryotic microorganisms; rapidly adapting to various environments and external stressors, evolving resistance and exhibiting diverse strategies of pathogenesis. This combined with limited targets for selective fungicidal drugs has resulted in an increasing frequency of fungal infections. We now know that 80% of chronic wounds contain fungi, often associated with diverse microbial communities. Owing to this growing prevalence, the global market for anti-fungal drugs is predicted to reach $ 16.1 billion in 2021. Exciton Technologies Inc. has developed a stabilized drug delivery system for higher oxidation state silver, Ag(III) compounds, with potent topical antimicrobial with antibiofilm activity. This active ingredient has demonstrated 10 to 100-fold greater activity vs. leading silver and conventional antibiotic therapies and has exhibited biocidal activity against antibiotic resistant bacterial strains without harming humans. Precursory evidence of the efficacy of Ag(III) compounds against fungi, including Candida albicans and Aspergillus niger, has been observed in planktonic cultures in-vitro. However, the targets of this activity are not known for Ag(III) compounds. The objectives of this research project are to elucidate the biological targets of Ag(III) compounds in fungal microorganisms, differentiating the mechanisms of action from conventional antifungal drugs. This project will utilize transcriptional deletion libraries of C. albicans in combination with spectroscopic assays for the assessment and evaluation of silver interventions, gaining insight into the management of fungal infections in chronic wounds. Substantiating the effectiveness of Ag(III) compounds as topical therapeutic agents will help capture a growing segment of the antifungal market.