Metabolism in Fungal Pathogenesis

Abstract

Fungal pathogens must assimilate local nutrients to establish an infection in their mammalian host. We focus on carbon, nitrogen, and micronutrient assimilation mechanisms, discussing how these influence host -fungus interactions during infection. We highlight several emerging trends based on the available data. First, the perturbation of carbon, nitrogen, or micronutrient assimilation attenuates fungal pathogenicity. Second, the contrasting evolutionary pressures exerted on facultative versus obligatory pathogens have led to contemporary pathogenic fungal species that display differing degrees of metabolic flexibility. The evolutionarily ancient metabolic pathways are conserved in most fungal pathogen, but interesting gaps exist in some species (e.g., Candida glabrata). Third, metabolic flexibility is generally essential for fungal pathogenicity, and in particular, for the adaptation to contrasting host microenvironments such as the gastrointestinal tract, mucosal surfaces, bloodstream, and internal organs. Fourth, this metabolic flexibility relies on complex regulatory networks, some of which are conserved across lineages, whereas others have undergone significant evolutionary rewiring. Fifth, metabolic adaptation affects fungal susceptibility to antifungal drugs and also presents exciting opportunities for the development of novel therapies. N utrient assimilation is a central and fundamental prerequisite for the growth and survival of all living organisms. Pathogenic fungi inhabit dynamic and contrasting niches and must display rapid and effective adaptation to changes in nutrient availability in these microenvironments. To achieve this, they regulate specific nutrient uptake mechanisms and modulate their metabolism, displaying an impressive degree of metabolic flexibility. This metabolic flexibility, which enhances the fitness of the fungus, is often as essential for pathogenicity as virulence factors, thereby representing an attractive target for potential therapeutic intervention.The major fungal pathogens of humans have evolved in a polyphyletic manner (i.e., pathogenicity has emerged independently in different

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The Candida albicans ATO Gene Family Promotes Neutralization of the Macrophage Phagolysosome

“…Acquisition and utilization of available nutrients from the host is fundamental to the survival and pathogenicity of microorganisms, and the host uses nutrient deprivation and sequestration as a defense mechanism to limit microbial growth. Pathogens have to identify ready sources of nutrients in a host, and it is clear that some are scarce, such as nucleotides and iron, since mutants impaired in the synthesis or uptake of these compounds are avirulent in many pathogens (47)(48)(49). In contrast, amino acids appear abundant, since many (but not all) auxotrophic mutants retain full virulence (4,50,51).…”

Robust Extracellular pH Modulation by Candida albicans during Growth in Carboxylic Acids

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