Urease metabolism in the wheat pathogen Zymoseptoria tritici

病原真菌能够感知和调节其环境的pH值。这确保了局部pH对于它们的生长和分泌的毒力因子的活性是最佳的。病原体对pH值的操纵也可能对宿主产生全面免疫应答的能力产生不利影响。真菌在催化含氮化合物的过程中产生氨，氨的产生导致当地环境的碱化。氨被多种植物和动物真菌病原体用于调节pH，例如番茄病原体胶孢炭疽菌（Colletotrichum gloeosporioides）和人类病原体白色念珠菌。尿素酶是一种重要的pH调节剂，因为它将尿素转化为氨和二氧化碳，并且是人类真菌病原体新型隐球菌和波氏球孢子菌的毒力所必需的。我们感兴趣的是确定在何种程度上尿素酶是一个一般的真菌毒力因子，由于其作为抗真菌靶点的潜力。尿素酶是唯一已知的含镍真核生物酶，尿素酶成熟涉及多种辅助蛋白。这种复杂性为脲酶失活提供了许多靶点。我们的特点方面的尿素酶成熟的C。neoformans，并在此项目期间将进行类似的研究，小麦病原菌Zymoseptoria triumph。我们的初步研究表明，Z。三尖杉酯酶是一种尿素酶阳性微生物。我们将检验Z.三唑醇调节该真菌的外部pH，并且该过程是该重要病原体的毒力所需的。学生将使用一系列的分子技术来研究尿素代谢和Z的毒力。缺乏尿素酶和其成熟所需的辅助蛋白质的突变体。对Z.还将建造三氧化二脲和镍运输船。该项目福尔斯属于BBSRC的农业和食品安全战略优先事项。在世界范围内，小麦是人类食物中植物蛋白的主要来源，因此保护这种食物来源的供应至关重要。令人关注的是感染小麦并降低农业产量的真菌病原体。z.三叶草引起全世界发生的三叶草壳针孢斑点病，在发展中国家可能是一个严重的问题。在严重的流行病中，小麦产量可减少高达50%。三孢壳针孢菌斑点病是欧洲和英国最严重的小麦病害，每年造成5000万英镑的经济损失。虽然有几种杀菌剂被用来控制Z。最近，许多种群已经进化出杀真菌剂抗性，因此需要新的杀真菌剂靶标。了解尿素酶在Z.该研究将有助于开发控制这种重要病原体的新策略

Pathogenic fungi are able to sense and modulate the pH of their environment. This ensures that the local pH is optimal for their growth and the activity of secreted virulence factors. Manipulation of pH by pathogens can also have a detrimental impact on the ability of the host to raise a full immune response. Fungi produce ammonia during the catabolism of nitrogenous compounds and its generation results in alkalinisation of the local environment. Ammonia is used to modulate pH by a diverse range of plant and animal fungal pathogens such as the tomato pathogen Colletotrichum gloeosporioides and the human pathogen Candida albicans. The urease enzyme is an important pH regulator as it converts urea into ammonia and carbon dioxide and is required for the virulence of the human fungal pathogens Cryptococcus neoformans and Coccidioides posadasii. We are interested in determining to what extent urease is a general fungal virulence factor due to its potential as an antifungal target. Urease is the only known nickel containing eukaryotic enzyme and urease maturation involves multiple accessory proteins. This complexity provides many targets for urease inactivation. We have characterised aspects of urease maturation in C. neoformans and during this project will undertake similar studies in the wheat pathogen Zymoseptoria tritici. Our preliminary studies have established that Z. tritici is a urease positive organism. We will test the hypothesis that the urease activity of Z. tritici modulates the external pH of this fungus and that this process is required for the virulence of this important pathogen. The student will use a range of molecular techniques to study urea metabolism and the virulence of Z. tritici mutants lacking urease and the accessory proteins required for its maturation. Structural studies of the Z. tritici urea and nickel transporters will also be undertaken. This project falls within the BBSRC strategic priority of agriculture and food safety. Worldwide, wheat is the major source of vegetable protein in human food so it is essential that the supply of this food source is protected. Of concern are fungal pathogens that infect wheat and reduce agricultural yields. Z. tritici causes septoria tritici blotch disease that occurs throughout the world and can be a significant problem in developing countries. In severe epidemics wheat yields can be reduced by up to 50%. Septoria tritici blotch disease is the most serious wheat disease in Europe and in the UK results in an annual financial loss of £50 million. Although several fungicides are used to control Z. tritici many populations have evolved fungicide resistance so that new fungicidal targets are needed. Understanding the role of the urease enzyme during the infection cycle of Z. tritici will help in the development of new strategies to control this important pathogen