Paracoccidioides spp. catalases and their role in antioxidant defense against host defense responses

Abstract

Dimorphic human pathogenic fungi interact with host effector cells resisting their microbicidal mechanisms. Yeast cells are able of surviving within the tough environment of the phagolysosome by expressing an antioxidant defense system that provides protection against host-derived reactive oxygen species (ROS). This includes the production of catalases (CATs). Here we identified and analyzed the role of CAT isoforms in Paracoccidioides, the etiological agent of paracoccidioidomycosis. Firstly, we found that one of these isoforms was absent in the closely related dimorphic pathogen Coccidioides and dermatophytes, but all of them were conserved in Paracoccidioides, Histoplasma and Blastomyces species. We probed the contribution of CATs in Paracoccidioides by determining the gene expression levels of each isoform through quantitative RT-qPCR, in both the yeast and mycelia phases, and during the morphological switch (transition and germination), as well as in response to oxidative agents and during interaction with neutrophils. PbCATP was preferentially expressed in the pathogenic yeast phase, and was associated to the response against exogenous H2O2. Therefore, we created and analyzed the virulence defects of a knockdown strain for this isoform, and found that CATP protects yeast cells from H2O2 generated in vitro and is relevant during lung infection. On the other hand, CATA and CATB seem to contribute to ROS homeostasis in Paracoccidioides cells, during endogenous oxidative stress. CAT isoforms in Paracoccidioides might be coordinately regulated during development and dimorphism, and differentially expressed in response to different stresses to control ROS homeostasis during the infectious process, contributing to the virulence of Paracoccidioides.

Differential Metabolism of a Two-Carbon Substrate by Members of the Paracoccidioides Genus

“…Catalase and peroxidase catabolize H 2 O 2 . Paracoccidioides isolates encode three catalases, PbCatA, PbCatP , and PbCatB , which catalyze the decomposition of H 2 O 2 into oxygen and water (Chagas et al, 2008 ; Tamayo et al, 2017 ). CATP was up-regulated in all isolates of Paracoccidioides (Figure 8 ).…”

Down-regulation of TUFM impairs host cell interaction and virulence by Paracoccidioides brasiliensis

“…Colony formation was monitored at 36 °C for 15–20 days. The phenotypic stability of the transformants was assessed by consecutive (at least three times) subculturing in BHI medium nonselective and then again in medium non-selective and selective medium with hygromycin B (150 μg mL −1 ) for three consecutive times at 36 °C 63,69 .…”

ParacoccidioidesSpp.: Virulence Factors and Immune-Evasion Strategies

“…Furthermore, Tamayo et al [ 156 ] recently identified and characterized the three members of the catalase (CAT) gene family in different fungal strains of Paracoccidioides spp., covering each phylogenetic lineage, as well as in other Onygenales. This study revealed that Coccidioides and dermatophyte genomes do not encode the extracellular catalase CATB, suggesting that Onygenales may have evolved different mechanisms to counteract oxidative stress via catalases.…”