Identification and analysis of the role of superoxide dismutases isoforms in the pathogenesis of Paracoccidioides spp.
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2016
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The ability of Paracoccidioides to defend itself against reactive oxygen species (ROS) pro duced by host effector cells is a prerequisite to survive. To counteract these radicals, Para coccidioides 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 phyloge netic 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 inter action. 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 intra cellular requirements of the fungus. Altogether, our data suggests that P. brasiliensis
actively responds to the radicals generated endogenously during metabolism and counter acts the oxidative burst of immune cells by inducing the expression of SOD isoforms.
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TAMAYO, Diana et al. Identification and analysis of the role of superoxide dismutases isoforms in the pathogenesis of Paracoccidioides spp. PLoS Neglected Tropical Diseases, San Francisco, v. 10, e0004481, 2016. DOI: 10.1371/journal.pntd.0004481. Disponível em: https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0004481. Acesso em: 25 nov. 2024.