Nutritional adaptation by fungal pathogens

Fungal pathogens display a variety of life styles in terms of nutritional adaptation to the host environment. For example, some of the most devastating plant pathogens are biotrophs that are obligately dependent on nutrient acquisition from living hosts. The maize pathogen Ustilago maydis is a useful model for investigating biotrophy because this species can be grown in culture but is obligately dependent on plant infection to complete the sexual phase of its life cycle. We made use of published metabolic profiling of diseased maize tissue to hypothesize that U. maydis responds to combinations of different nutrients to support biotrophic growth. A test of this hypothesis revealed that combinations of carbon sources trigger phenotypes associated with biotrophy. These phenotypes included the transcription of genes encoding effectors that are usually only expressed during biotrophic development, and the formation of melanin associated with sporulation in plant tumors. Additionally, we found that oxygen sensing is important for the response to mixtures of carbon sources. These findings provide insights into the metabolic basis of fungal biotrophy. In a separate study, we examined the ability of the opportunistic human pathogen Cryptococcus neoformans to adapt to the iron- limited environment during cryptococcosis in vertebrate hosts. Iron withholding is a critical component of nutritional immunity in vertebrates, and C. neoformans responds to the low iron condition by elaborating a polysaccharide capsule that is a major virulence factor. Key acquisition mechanisms for iron include the activity of a high affinity iron permease/ferroxidase system and uptake of heme via endocytosis. The regulation of these functions is controlled by the iron-responsive transcription factors Cir1 and HapX in association with the monothiol glutaredoxin Grx4. A detailed analysis of Grx4 revealed contributions to a remarkable number of phenotypes and established connections between mitochondrial signals and virulence factor elaboration. Overall, an understanding of the response to specific nutrients may provide opportunities for antifungal intervention.