title: 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 H2O2generated 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.
authors.affiliation: Cellular and Molecular Biology Unit, Corporación para Investigaciones Biológicas, Medellín, Colombia; Institute of Biology, Universidad de Antioquia, Medellín, Colombia; School of Microbiology, Universidad de Antioquia, Medellín, Colombia.
authors.forename: Diana
authors.initials: D
authors.lastname: Tamayo
authors.affiliation: Cellular and Molecular Biology Unit, Corporación para Investigaciones Biológicas, Medellín, Colombia; Institute of Biology, Universidad de Antioquia, Medellín, Colombia; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
authors.forename: José F
authors.initials: JF
authors.lastname: Muñoz
authors.affiliation: Cellular and Molecular Biology Unit, Corporación para Investigaciones Biológicas, Medellín, Colombia; Department of Biological Sciences, School of Sciences, Universidad EAFIT, Medellín, Colombia; Instituto Universitario da Maia, Maia, Portugal.
authors.forename: Agostinho J
authors.initials: AJ
authors.lastname: Almeida
authors.affiliation: Cellular and Molecular Biology Unit, Corporación para Investigaciones Biológicas, Medellín, Colombia.
authors.forename: Juan D
authors.initials: JD
authors.lastname: Puerta
authors.affiliation: Cellular and Molecular Biology Unit, Corporación para Investigaciones Biológicas, Medellín, Colombia.
authors.forename: Ángela
authors.initials: Á
authors.lastname: Restrepo
authors.affiliation: Broad Institute of MIT and Harvard, Cambridge, MA, USA.
authors.forename: Christina A
authors.initials: CA
authors.lastname: Cuomo
authors.affiliation: Cellular and Molecular Biology Unit, Corporación para Investigaciones Biológicas, Medellín, Colombia; School of Medicine, Universidad de Antioquia, Medellín, Colombia.
authors.forename: Juan G
authors.initials: JG
authors.lastname: McEwen
authors.affiliation: Cellular and Molecular Biology Unit, Corporación para Investigaciones Biológicas, Medellín, Colombia; School of Microbiology, Universidad de Antioquia, Medellín, Colombia; MICROBA Research Group, School of Microbiology, Universidad de Antioquia, Medellín, Colombia. Electronic address: orville.hernandez@udea.edu.co.
authors.forename: Orville
authors.initials: O
authors.lastname: Hernández
mesh_terms: D000975:Antioxidants / Q000378:metabolism*; D002374:Catalase / Q000235:genetics / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D006658:Histoplasma / Q000235:genetics; D006801:Humans; D006861:Hydrogen Peroxide / Q000737:chemistry; D025282:Mycelium / Q000235:genetics; D018384:Oxidative Stress / Q000235:genetics*; D010228:Paracoccidioides / Q000201:enzymology; D010229:Paracoccidioidomycosis / Q000201:enzymology / Q000378:metabolism* / Q000382:microbiology; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D002374:Catalase
keywords: Antisense RNA; Catalases; Dimorphic fungal pathogens; Endogenous and exogenous ROS; Paracoccidioides spp.; Peroxide