Transcriptional and Proteomic Responses to Carbon Starvation in Paracoccidioides (original) (raw)
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Differential Metabolism of a Two-Carbon Substrate by Members of the Paracoccidioides Genus
Frontiers in microbiology, 2017
The genus Paracoccidioides comprises known fungal pathogens of humans and can be isolated from different infection sites. Metabolic peculiarities in different members of the Paracoccidioides led us to perform proteomic studies in the presence of the two-carbon molecule acetate, which predominates in the nutrient-poor environment of the phagosome. To investigate the expression rates of proteins of different members of Paracoccidioides, including one isolate of P. lutzii (Pb01) and three isolates of P. brasiliensis (Pb03, Pb339, and PbEPM83), using sodium acetate as a carbon source, proteins were quantified using label-free and data-independent liquid chromatography-mass spectrometry. Protein profiles of the isolates were statistically analyzed, revealing proteins that were differentially expressed when the fungus was cultivated in a non-preferential carbon source rather than glucose. A total of 1,160, 1,211, 1,280, and 1,462 proteins were reproducibly identified and relatively quanti...
PLoS neglected tropical diseases, 2015
Hypoxic microenvironments are generated during fungal infection. It has been described that to survive in the human host, fungi must also tolerate and overcome in vivo microenvironmental stress conditions including low oxygen tension; however nothing is known how Paracoccidioides species respond to hypoxia. The genus Paracoccidioides comprises human thermal dimorphic fungi and are causative agents of paracoccidioidomycosis (PCM), an important mycosis in Latin America. In this work, a detailed hypoxia characterization was performed in Paracoccidioides. Using NanoUPLC-MSE proteomic approach, we obtained a total of 288 proteins differentially regulated in 12 and 24 h of hypoxia, providing a global view of metabolic changes during this stress. In addition, a functional characterization of the homologue to the most important molecule involved in hypoxia responses in other fungi, the SREBP (sterol regulatory element binding protein) was performed. We observed that Paracoccidioides species...
Journal of Biological Chemistry, 2005
Paracoccidioides brasiliensis is the causative agent of paracoccidioidomycosis, a disease that affects 10 million individuals in Latin America. This report depicts the results of the analysis of 6,022 assembled groups from mycelium and yeast phase expressed sequence tags, covering about 80% of the estimated genome of this dimorphic, thermo-regulated fungus. The data provide a comprehensive view of the fungal metabolism, including overexpressed transcripts, stage-specific genes, and also those that are up-or down-regulated as assessed by in silico electronic subtraction and cDNA microarrays. Also, a significant differential expression pattern in mycelium and yeast cells was detected, which was confirmed by Northern blot analysis, providing insights into differential metabolic adaptations. The overall transcriptome analysis provided information about sequences related to the cell cycle, stress response, drug resistance, and signal transduction pathways of the * This work was supported by MCT, CNPq, CAPES, FUB, UFG, and FUNDECT-MS. □ S The on-line version of this article (available at http://www.jbc.org) contains nine additional tables.
General metabolism of the dimorphic and pathogenic fungus Paracoccidioides brasiliensis
2005
Paracoccidioides brasiliensis has set the grounds for a global understanding of its metabolism in both mycelium and yeast forms. This fungus is able to use the main carbohydrate sources, including starch, and it can store reduced carbons in the form of glycogen and trehalose; these provide energy reserves that are relevant for metabolic adaptation, protection against stress and infectivity mechanisms. The glyoxylate cycle, which is also involved in pathogenicity, is present in this fungus. Classical pathways of lipid biosynthesis and degradation, including those of ketone body and sterol production, are well represented in the database of P. brasiliensis. It is able to synthesize de novo all nucleotides and amino acids, with the sole exception of asparagine, which was confirmed by the fungus growth in minimal medium. Sulfur metabolism, as well as the accessory synthetic pathways of vitamins and co-factors, are likely to exist in this fungus.
Updates in Paracoccidioides Biology and Genetic Advances in Fungus Manipulation
Journal of Fungi, 2021
The dimorphic fungi of the Paracoccidioides genus are the causative agents of paracoccidioidomycosis (PCM). This disease is endemic in Latin America and primarily affects workers in rural areas. PCM is considered a neglected disease, despite being a disabling disease that has a notable impact on the public health system. Paracoccidioides spp. are thermally dimorphic fungi that present infective mycelia at 25 °C and differentiate into pathogenic yeast forms at 37 °C. This transition involves a series of morphological, structural, and metabolic changes which are essential for their survival inside hosts. As a pathogen, the fungus is subjected to several varieties of stress conditions, including the host immune response, which involves the production of reactive nitrogen and oxygen species, thermal stress due to temperature changes during the transition, pH alterations within phagolysosomes, and hypoxia inside granulomas. Over the years, studies focusing on understanding the establishm...
Transcriptomic reprogramming of genus Paracoccidioides in dimorphism and host niches
Fungal genetics and biology : FG & B, 2014
The thermodimorphic fungi Paracoccidioides brasiliensis and Paracoccidioides lutzii are the etiologic agents of Paracoccidioidomycosis (PCM), the most important endemic systemic mycosis in Latin America. Paracoccidioides grows as saprophytic mycelia that produce infective conidia propagules, which are inhaled into the lungs where the fungus converts to the pathogenic yeast form. From the lungs, Paracoccidioides may disseminate through blood and lymphatics to several other organs and tissues. During the last decade we have witnessed the generation of a large amount of transcriptomic data regarding the events leading to the morphological transition and host niche adaptation. In this review we summarize those findings and discuss the consequence of gene expression plasticity in the persistence and survival of this pathogen. In addition, we discuss the future trends on the host-pathogen studies and how new molecular strategies, such as RNA-seq, dual RNA-seq and Chip-Seq can be powerful ...
Mycopathologia, 2008
Paracoccidioiddes brasiliensis is a thermo-dimorphic fungus endemic to Latin America, where it causes the most prevalent systemic mycosis, paracoccidioidomycosis (PCM). DNA microarray technology has been used to identify patterns of gene expression when a microbe is confronted with conditions of interest, such as in vitro and/or ex vivo interaction with specific cells. P. brasiliensis is one organism that has benefited from this approach. Even though its genome has not been sequenced yet, much has been discovered from its transcriptome and DNA array analyses. In this review, we will outline the current knowledge in P.␣brasiliensis transcriptome, with focus on differential expression analysis in vitro and on the discussion of the genes that are controlled during the host–pathogen interaction ex vivo in order to give insights into the pathobiology of this fungus. In vitro experiments enabled the delineation of whole metabolic pathways; the description of differential metabolism between mycelium and yeast cells and of the mainly signaling pathways controlling dimorphism, high temperature growth, thermal and oxidative stress, and virulence/pathogenicity. Recent ex vivo experiments provided advances on the comprehension of the plasticity of response and indicate that P. brasiliensis is not only␣able to undergo fast and dramatic expression profile changes but can also discern subtle differences,␣such as whether it is being attacked by a macrophage or submitted to the bloodstream route conditions.
Functional genome of the human pathogenic fungus Paracoccidioides brasiliensis
Fems Immunology and Medical Microbiology, 2005
Paracoccidioides brasiliensis is a dimorphic and thermo-regulated fungus which is the causative agent of paracoccidioidomycosis, an endemic disease widespread in Latin America. Pathogenicity is assumed to be a consequence of the cellular differentiation process that this fungus undergoes from mycelium to yeast cells during human infection. In an effort to elucidate the molecular mechanisms involved in this process a network of Brazilian laboratories carried out a transcriptome project for both cell types. This review focuses on the data analysis yielding a comprehensive view of the fungal metabolism and the molecular adaptations during dimorphism in P. brasiliensis from analysis of 6022 groups, related to expressed genes, which were generated from both mycelium and yeast phases.
Functional genome of the human pathogenic fungusParacoccidioides brasiliensis
Fems Immunology and Medical Microbiology, 2005
Paracoccidioides brasiliensis is a dimorphic and thermo-regulated fungus which is the causative agent of paracoccidioidomycosis, an endemic disease widespread in Latin America. Pathogenicity is assumed to be a consequence of the cellular differentiation process that this fungus undergoes from mycelium to yeast cells during human infection. In an effort to elucidate the molecular mechanisms involved in this process a network of Brazilian laboratories carried out a transcriptome project for both cell types. This review focuses on the data analysis yielding a comprehensive view of the fungal metabolism and the molecular adaptations during dimorphism in P. brasiliensis from analysis of 6022 groups, related to expressed genes, which were generated from both mycelium and yeast phases.