Recovery of the Paracoccidioides brasiliensis virulence after animal passage promotes changes in the antioxidant repertoire of the fungus

Abstract

Paracoccidioides brasiliensis is the agent of paracoccidioidomycosis (PCM), a cause of disease in healthy and immunocompromised persons in Latin America. The infection begins after inhalation of the fungal propagules and their thermo-dimorphic shift to yeast form. The development of the disease depends on factors associated with the host immune response and the infectious agent's characteristics, especially virulence. The oxidative stress response is an important virulence attribute in several fungi. In this study, we assessed the enzymatic repertoire of responses to oxidative stress in the Pb18 isolate with different degrees of virulence. The virulence of attenuated Pb18 (aPb18) strain was recovered after several animal passages. Virulent strain (vPb18) showed an effective fungal oxidative stress response and several genes involved in response to oxidative stress were up-regulated in this isolate. These genes expressed the same profile when we recovered the phenotypic virulence in attenuated strain aPb18. Our study demonstrated that attenuated P. brasiliensis recovered their virulence after serial animal passages (vPb18), and this process positively modulated the fungus's antioxidant repertoire.

Updates in Paracoccidioides Biology and Genetic Advances in Fungus Manipulation

“…Gene expression and enzymatic activity showed the distinct responses of antioxidant enzymes between virulent and attenuated isolates. Notably, the P. brasiliensis attenuated isolate recovered the virulent phenotype and the antioxidant repertoire after animal passages [138].…”

Effect of Nitrosative Stress on the S-Nitroso-Proteome of Paracoccidioides brasiliensis

“…The activity of Cu-Zn-superoxide dismutase (SOD) was analyzed colorimetrically at 560-nm wavelength by measuring the reduction of nitroblue tetrazolium (NBT) by superoxide radicals, which were generated from PMS reduction mediated by β-NADH, where 1 unit is the SOD amount necessary to inhibit 50% of the initial rate of NBT reduction Ewing and Janero, 1995;Castilho et al, 2018). The activity of catalase (CAT) was determined by monitoring the decrease in absorbance at 240 nm wavelength of the rate of hydrogen peroxide decomposition (Aebi, 1984).…”

The Human Pathogen Paracoccidioides brasiliensis Has a Unique 1-Cys Peroxiredoxin That Localizes Both Intracellularly and at the Cell Surface

“…In C. albicans , the Prx1 ortholog (Tsa1) is found in the cell wall specifically in the pathogenic hyphal phase, while the protein localizes in the cytosol and nucleus of yeast cells, pointing to a role in pathogenicity (Urban et al, 2003 ). In P. brasiliensis , attenuated yeast cells recovered their virulence after serial passages in mice and this process positively modulated the fungal antioxidant repertoire (Castilho et al, 2018 ). Additionally, proteins involved in the oxidative stress response in P. brasiliensis yeast cells were up-regulated during macrophage infection (Parente-Rocha et al, 2015 ).…”