description
- 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