Defining the role of phosphate metabolism in promoting stress resistance and virulence in fungal pathogens

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The ability of pathogenic fungi to adapt to stresses encountered within different host niches is essential for virulence. Recently, we have found that phosphate homeostasis, regulated by the Pho4 transcription factor, is vital for the resistance of the fungal pathogen, Candida albicans, to diverse and physiologically important stresses encountered during infection. Furthermore, we have found that many of the stress-sensitive phenotypes exhibited by pho4 delta cells, such as to metal cation and superoxide stresses, relate to the impact of phosphate metabolism on metal homeostasis. As Pho4 is vital for C. albicans pathogenesis, these findings provide new insight into how metabolic adaptation promotes C. albicans survival in the face of host-imposed stresses. However we know little regarding the regulation of Pho4 in C. albicans, or the mechanism(s) by which intracellular phosphate levels impact on metal homeostasis resulting in resistance to diverse stresses. In this project, we will define the regulatory network underlying phosphate acquisition strategies in C. albicans and investigate the mechanisms linking phosphate to metal homeostasis and stress resistance. This is important as our data strongly indicates that perturbation of phosphate acquisition strategies in pathogenic fungi could represent a novel therapeutic strategy to attenuate virulence. The project therefore fits with the BBSRC's strategic research priority of "Basic bioscience underpinning health". We predict that the research outcomes generated in C. albicans can also be transferred onto important plant fungal pathogens. Stress tolerance and metal acquisition strategies are also important virulence determinants in many plant pathogens such as the rice blast fungus Magnaporthe grisea and the corn smut fungus Ustilago maydis. Given the increasing threat to food security by such pathogens this project also applies to the research priority "Agriculture and food security".