The genus Aspergillus, which includes almost 200 species, has a tremendous impact on public health both beneficially as the workhorse of industrial applications and negatively as plant and human pathogens. The most serious disease caused by A. fumigatus is invasive aspergillosis (IA). IA occurs most commonly when susceptible individuals inhale conidia. These may germinate in the lung resulting in hyphal outgrowth that penetrates epithelial and endothelial barriers. The incidence of invasive infection in immunocompromised individuals is greater than 50% and often the death rate from 50 to 100%. Iron is an essential micronutrient for all eukaryotes, since it participates in a variety of essential biological processes and many studies have shown that iron is essential for growth and virulence of A. fumigatus. However, the bioavailability of this metal is low inside the host. As a consequence, A. fumigatus and other pathogenic micro-organisms have developed high affinity acquisition mechanisms to obtain iron during infection: reductive iron assimilation (RIA) and siderophore-mediated iron acquisition. A collection of A. fumigatus mutants of all genes encoding phosphatases was created and PhzA was identified as an important phosphatase involved in iron metabolism. Preliminary results showed that the mutant phzA is avirulent and displays reduced expression levels of genes involved in the biosynthesis of siderophores under conditions of shortage of iron and consequently the production of siderophore TAFC is also reduced. These unpublished data demonstrated the crucial role of phosphatase PhzA in the mechanism of iron acquisition during conditions of penury of this nutrient. Thus, we believe that the characterization of the pathways that are modulated by the phosphatase PhzA in A. fumigatus will provide opportunities for understanding how A. fumigatus regulates the use of iron for the establishment of infection. Furthermore, the identification of ligands and characterization of targets modulated directly or indirectly by this phosphatase will assist in composing a network of biological interactions that will promote the understanding of which are the major events in the signal transduction level that are important for establishment of infection by A. fumigatus.
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