Nutrition-Associated Processes Govern Fungal Pathogenicity

Abstract Fungal pathogens present a major common threat across human communities: they cause disease and death in humans, animals, and global food crops. The development of anti-fungal therapies is hampered primarily by the lack of knowledge about the molecular mechanisms of fungal pathogenicity at the host-pathogen axis. Many studies have shown that nutrition-associated processes such as autophagy and metal homeostasis play essential roles in fungal virulence during systemic infection. During infection, the host immune system often employs nutrition restriction mechanisms to limit microbial proliferation and facilitate the killing and elimination of invading pathogens. Therefore, fast sensing and adaptation to the levels of environmental nutrients are critical if the fungal pathogen is to survive, replicate, and colonize in the host. Fungal cells have evolved numerous precise mechanisms to respond to various levels of nutrient availability. Studies show that fungal cells manipulate the expression of genes involved in nutrient acquisition, autophagosome formation, toxic nutrient detoxification, or cell morphological transition to counter the anti-fungal strategies of the host. This review of the most recent studies of nutrition-related pathways focuses primarily on autophagy, metal homeostasis, and the nutrition-driven morphological switches found in two major human fungal pathogens, Cryptococcus neoformans and Candida albicans. It is a systematic comparison of the functional divergence of nutrition-related genes in the fungal pathogenicity of these evolutionarily distinct but related fungal species.