SIDEROPHORE-MEDIATED IRON UPTAKE IN PARACOCCIDIOIDES BRASILIENSIS

Mirelle Garcia Silva (UFG); Elisa Flávia Luiz Cardoso Bailão (UFG); Alexandre Melo Bailão (UFG); Célia Maria de Almeida Soares (UFG)

Iron is an essential nutrient for all eukaryotes and nearly all prokaryotes. It is indispensable for a variety of cellular process including respiration, synthesis of amino acids and lipids, and acts as a cofactor of many enzymes. Most of pathogens, like fungi, have specific mechanisms for iron uptake from their hosts, in which the availability of this ion is extremely low. Low-affinity systems of iron uptake are activated when iron is abundant, whereas high-affinity systems are important under iron-limiting conditions. The siderophore-mediated iron uptake is a type of non-reductive high-affinity system. Siderophores are high-affinity ferric-ion specific chelators with low-molecular weight. Their biosynthesis is controlled by iron availability. These molecules are secreted to mobilize extracellular iron or are produced intracellularly for iron storage. The goal of this work is to investigate the siderophore-mediated iron uptake in Paracoccidioides brasiliensis, the aetiological agent of the most prevalent human systemic mycosis in Latin America. In silico screening at P. brasiliensis structural genome (http://www.broadinstitute.org/annotation/genome/paracoccidioides_brasiliensis/MultiHome.html) was performed in order to identify genes related to iron uptake by the non-reductive pathway. This analysis allowed the design of a model containing genes related to siderophore biosynthesis and transport, suggesting that this mechanism is used by the fungus to capture iron under iron-limiting conditions. Aiming to analize the relative expression of these genes, P. brasiliensis cells were grown in iron depleted liquid medium and then transferred to liquid medium supplemented with different concentrations of this metal. The relative expression of the siderophore biosynthesis gene sidA and siderophore transport gene sit1 decreased in the iron containing medium, suggesting that their expression is regulated by iron availability. The siderophore production as well as the classification of the siderophores produced by this pathogen are being carried out. As the limitation of iron availability is a defense strategy of many hosts, the siderophore non-reductive pathway iron acquisition system could be a virulence factor of P.brasiliensis.