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

阐明真菌病原体中氧化银的生物靶标****

• 批准号: 537055-2018
• 负责人: Shapiro, Rebecca
• 金额: $ 1.82万
• 依托单位: University of Guelph
• 依托单位国家: 加拿大
• 项目类别: Engage Grants Program
• 财政年份: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=664883
• 关键词: Elucidating; biological; targets; oxidized; silver

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.

真菌是具有高度弹性的微生物真核微生物;快速适应各种环境和外部压力，进化抗性并表现出不同的致病策略。这与选择性杀真菌药物的有限目标相结合，导致真菌感染的频率增加。我们现在知道，80%的慢性伤口含有真菌，通常与不同的微生物群落有关。由于这种日益增长的流行率，预计2021年全球抗真菌药物市场将达到161亿美元。激子科技公司已开发出一种稳定的药物输送系统，用于更高氧化态的银、Ag（III）化合物，具有具有抗菌膜活性的强效局部抗菌剂。这种活性成分的活性比领先的银和传统抗生素疗法高10至100倍，并且对抗生素耐药细菌菌株表现出杀菌活性，而不会伤害人类。Ag（III）化合物对真菌（包括白色念珠菌和尼日尔曲霉）的功效的前兆证据已经在体外培养物中观察到。然而，这种活性的目标是未知的银（III）化合物。本研究项目的目的是阐明Ag（III）化合物在真菌微生物中的生物靶点，区分其与常规抗真菌药物的作用机制。本项目将利用C.白色念珠菌与光谱分析相结合，用于评估和评价银干预，深入了解慢性伤口真菌感染的管理。证实Ag（III）化合物作为局部治疗剂的有效性将有助于占领日益增长的抗真菌市场。