AUTHOR=Silva Mirelle G., Schrank Augusto , Bailão Elisa Flávia L., Bailão Alexandre M., Borges Clayton L., Staats Charley C., Parente Juliana A., Pereira Maristela , Salem-Izacc Silvia M., Mendes-Giannini Maria José S., Zancopé-Oliveira Rosely M., Rosa E Silva Lívia K., Nosanchuk Joshua D., Vainstein Marilene H., Soares Célia M.

TITLE=The Homeostasis of Iron, Copper, and Zinc in Paracoccidioides Brasiliensis, Cryptococcus Neoformans Var. Grubii, and Cryptococcus Gattii: A Comparative Analysis

JOURNAL=Frontiers in Microbiology

VOLUME=2

YEAR=2011

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2011.00049

DOI=10.3389/fmicb.2011.00049

ISSN=1664-302X

ABSTRACT=<p>Iron, copper, and zinc are essential for all living organisms. Moreover, the homeostasis of these metals is vital to microorganisms during pathogenic interactions with a host. Most pathogens have developed specific mechanisms for the uptake of micronutrients from their hosts in order to counteract the low availability of essential ions in infected tissues. We report here an analysis of genes potentially involved in iron, copper, and zinc uptake and homeostasis in the fungal pathogens <italic>Paracoccidioides brasiliensis</italic>, <italic>Cryptococcus neoformans</italic> var. <italic>grubii</italic>, and <italic>Cryptococcus gattii</italic>. Although prior studies have identified certain aspects of metal regulation in <italic>Cryptococcus</italic> species, little is known regarding the regulation of these elements in <italic>P. brasiliensis</italic>. We also present amino acid sequences analyses of deduced proteins in order to examine possible conserved domains. The genomic data reveals, for the first time, genes associated to iron, copper, and zinc assimilation and homeostasis in <italic>P. brasiliensis</italic>. Furthermore, analyses of the three fungal species identified homologs to genes associated with high-affinity uptake systems, vacuolar and mitochondrial iron storage, copper uptake and reduction, and zinc assimilation. However, homologs to genes involved in siderophore production were only found in <italic>P. brasiliensis</italic>. Interestingly, <italic>in silico</italic> analysis of the genomes of <italic>P. brasiliensis</italic><italic>Pb</italic>01, <italic>Pb</italic>03, and <italic>Pb</italic>18 revealed significant differences in the presence and/or number of genes involved in metal homeostasis, such as in genes related to iron reduction and oxidation. The broad analyses of the genomes of <italic>P. brasiliensis</italic>, <italic>C. neoformans</italic> var. <italic>grubii</italic>, and <italic>C. gattii</italic> for genes involved in metal homeostasis provide important groundwork for numerous interesting future areas of investigation that are required in order to validate and explore the function of the identified genes and gene pathways.</p>