Virulence factors of fungal pathogens

真菌病原体的毒力因子

• 批准号: 105704-2012
• 负责人: Moore, Margo
• 金额: $ 2.48万
• 依托单位: Simon Fraser University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=569103
• 关键词: Virulence; factors; fungal; pathogens

Fungi are important in biotechnology, agriculture and in medicine. Aspergillus species and members of the group Mucorales are filamentous fungi (moulds) that may cause life-threatening disease in susceptible people. Immunosuppressed individuals are at highest risk. Exposure is via airborne fungal spores followed by growth of the fungus in the lung. In some cases, the fungi may spread to other organs such as the brain. Mortality from these infections ranges from 30-80%. Our research is focussed on two aspects of fungal biology: 1) the role of specific sugars present on the fungal spores, called sialic acids, in the adherence of spores to lung tissue, and 2) how fungi acquire iron from the host. During previous NSERC funding, we identified the enzyme in Aspergillus fumigatus that releases sialic acids from tissue. We also showed that iron uptake by Aspergillus fumigatus is mediated by small iron chelators called siderophores, and that siderophore synthesis by fungi is absolutely required for virulence. We characterized the proteins involved in siderophore synthesis and uptake to determine how these proteins bring iron into the fungal cell. We propose to continue working on both of these topics. Specifically, we will probe the role of sialic acids by creating mutant strains that have have no sialic acids on the spore surface. In addition, we will examine the importance of siderophores in the survival of Mucorales and in another species of Aspergillus called Aspergillus terreus. This work will expand our knowledge of the biology of filamentous fungi. A better understanding of the processes of iron acquisition and sialic acid synthesis may ultimately lead to the improvements in the use of these fungi for biotechnology, and in the development of novel, effective antifungal agents.

真菌在生物技术、农业和医学中很重要。曲霉属物种和毛霉目（Mucorales）的成员是丝状真菌（霉菌），可能导致易感人群发生危及生命的疾病。免疫抑制的人处于最高风险。暴露是通过空气中的真菌孢子，然后真菌在肺部生长。在某些情况下，真菌可能会扩散到其他器官，如大脑。这些感染的死亡率为30- 80%。 我们的研究集中在真菌生物学的两个方面：1）真菌孢子上存在的特定糖（称为唾液酸）在孢子粘附于肺组织中的作用，以及2）真菌如何从宿主获得铁。 在之前的NSERC资助中，我们鉴定了烟曲霉中从组织中释放唾液酸的酶。我们还表明，烟曲霉铁的吸收介导的小铁螯合剂称为铁载体，铁载体合成真菌是绝对需要的毒力。我们表征了参与铁载体合成和摄取的蛋白质，以确定这些蛋白质如何将铁带入真菌细胞。 我们建议继续就这两个专题开展工作。具体来说，我们将通过创建孢子表面没有唾液酸的突变菌株来探索唾液酸的作用。此外，我们将研究铁载体在毛霉目和另一种曲霉属土曲霉中的生存的重要性。 这项工作将扩大我们对丝状真菌生物学的了解。更好地理解 铁的获取和唾液酸合成的过程可能最终导致这些真菌在生物技术中的应用的改进，以及新型有效抗真菌剂的开发。