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The ability of  Paracoccidioides  to defend itself against reactive oxygen species (ROS) produced by host effector cells is a prerequisite to survive. To counteract these radicals,  Paracoccidioides  expresses, among different antioxidant enzymes, superoxide dismutases (SODs). In this study, we identified six SODs isoforms encoded by the  Paracoccidioides  genome. We determined gene expression levels of representative isolates of the phylogenetic lineages of  Paracoccidioides  spp. (S1, PS2, PS3 and  Pb01-like ) using quantitative RT-PCR. Assays were carried out to analyze  SOD  gene expression of yeast cells, mycelia cells, the mycelia-to-yeast transition and the yeast-to-mycelia germination, as well as under treatment with oxidative agents and during interaction with phagocytic cells. We observed an increased expression of  PbSOD1  and  PbSOD3  during the transition process, exposure to oxidative agents and interaction with phagocytic cells, suggesting that these proteins could assist in combating the superoxide radicals generated during the host-pathogen interaction. Using  PbSOD1  and  PbSOD3  knockdown strains we showed these genes are involved in the response of the fungus against host effector cells, particularly the oxidative stress response, and in a mouse model of infection. Protein sequence analysis together with functional analysis of knockdown strains seem to suggest that  PbSOD3  expression is linked with a pronounced extracellular activity while  PbSOD1  seems more related to intracellular requirements of the fungus. Altogether, our data suggests that  P .  brasiliensis  actively responds to the radicals generated endogenously during metabolism and counteracts the oxidative burst of immune cells by inducing the expression of SOD isoforms.

Identification and Analysis of the Role of Superoxide Dismutases Isoforms in the Pathogenesis of Paracoccidioides spp.