Nitrogen, Iron, and Zinc Acquisition: Key Nutrients to Aspergillus fumigatus Virulence

Abstract

Aspergillus fumigatus is a ubiquitous soil decomposer and an opportunistic pathogen that is characterized by its large metabolic machinery for acquiring nutrients from media. Lately, an ever-increasing number of genes involved in fungal nutrition has been associated with its virulence. Of these, nitrogen, iron, and zinc metabolism-related genes are particularly noteworthy, since 78% of them have a direct implication in virulence. In this review, we describe the sensing, uptake and regulation process of the acquisition of these nutrients, the connections between pathways and the virulence-implicated genes. Nevertheless, only 40% of the genes mentioned in this review have been assayed for roles in virulence, leaving a wide field of knowledge that remains uncertain and might offer new therapeutic and diagnostic targets.

Urease of Aspergillus fumigatus Is Required for Survival in Macrophages and Virulence

“…It is noteworthy that nickel is a transition metal, like iron. Highly sophisticated mechanisms for the intracellular homeostasis maintenance of iron to balance its essentiality, low environmental availability, and cytotoxicity have been elucidated in A. fumigatus cells ( 8 , 56 ). It does not seem too farfetched that the acquisition, trafficking, and storage of nickel must be regulated in a similar way to allow for delivery to nickel-dependent proteins while avoiding toxic side effects.…”

“…In recent years, many virulence factors of A. fumigatus have been identified, and many of these are required to either interact with the host immune system or adapt to environmental stresses in the host ( 7 ). Additionally, an increasing number of genes that are involved in fungal nutrition (e.g., nitrogen metabolism-related genes) have been associated with A. fumigatus virulence ( 8 ).…”

The New GPI-Anchored Protein, SwgA, Is Involved in Nitrogen Metabolism in the Pathogenic Filamentous Fungus Aspergillus fumigatus

“…Nitrogen is an essential requirement for growth and fungi are able to use a wide variety of compounds as nitrogen sources. However, the use of different nitrogen compounds is selective, and readily assimilated nitrogen sources such as ammonium and glutamine are preferentially used [ 39 ]. In Aspergillus , the areA gene encodes the major nitrogen regulatory protein, which activates the transcription of many structural gene-encoding enzymes for nitrogen source catabolism under nitrogen-limiting conditions [ 40 ].…”

Pulmonary Aspergillosis in People with Cystic Fibrosis

“…fumigatus virulence is multifactorial and comprises genes, molecules, and properties involved in various processes, including but not limited to thermotolerance, cell wall composition and maintenance, meeting nutritional requirements, interactions with the host immune system, and stress response. 37,[42][43][44][45] A. fumigatus conidia disperse aerially and are inhaled frequently. Thus, the ability of conidia to adhere to host tissues is essential to A. fumigatus pathogenicity.…”

“…51 Like many other pathogens, A. fumigatus has developed several strategies to acquire nutrients from its host, with some of these being essential to virulence. 44,45 A. fumigatus obtains nutrients by secreting extracellular enzymes that degrade host tissues. Nitrogen metabolism has a much more significant role in A. fumigatus pathogenicity, with 23% of genes involved in the assimilation and metabolization of nitrogen required for virulence.…”