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Thiago Aparecido da Silva, Maria Cristina Roque-Barreira, Arturo Casadevall, Fausto Almeida
Extracellular vesicles (EVs) released by eukaryotes, archaea, and bacteria contain proteins, lipids, polysaccharides, and other molecules. The cargo analysis of EVs shows that they contain virulence factors suggesting a role in the pathogenesis of infection. The proteome, lipidome, RNA content, and carbohydrate composition of EVs from Paracoccidioides brasiliensis and Paracoccidioides lutzii were characterized. However, the effects of P. brasiliensis EVs on the host immune system have not yet been investigated...
October 24, 2016: Scientific Reports
Selwyn Arlington Headley, Lucienne Garcia Pretto-Giordano, Giovana Wingeter Di Santis, Lucas Alécio Gomes, Rafaela Macagnan, Daniela Farias da Nóbrega, Katherine Moura Leite, Brígida Kussumoto de Alcântara, Eiko Nakagawa Itano, Amauri Alcindo Alfieri, Mario Augusto Ono
Paracoccidioidomycosis (PCM) is an endemic disease of humans from Latin America that is caused by Paracoccidioides brasiliensis and P. lutzii, with most cases of PCM in domestic animals being associated with P. brasiliensis. This study presents the clinical, cytological, mycological, serological, and molecular findings associated with P. brasiliensis in a dog from Southern Brazil. Fine needle biopsies were collected from the skin and several lymph nodes of a 5-year-old female Labrador dog that had enlargement of most superficial lymph nodes...
October 18, 2016: Mycopathologia
Andrej Spec, Christopher R Barrios, Usama Ahmad, Laurie A Proia
Severe pulmonary or disseminated histoplasmosis often necessitates presumptive antifungal treatment while awaiting definitive diagnosis. Histoplasma antigen assays have improved sensitivity but results may lag up to 7 days. In order to increase diagnostic certainty, "soft clues" may be looked for in laboratory and radiologic data, such as elevated alkaline phosphatase or ferritin levels and findings of mediastinal adenopathy or hepatosplenomegaly. To determine if elevated aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio is specific to histoplasmosis or a non-specific marker for disseminated fungal infection or sepsis in general, we retrospectively examined records of all patients diagnosed with an endemic fungal infection (EFI) at Rush University Medical Center from January of 1997 to October of 2012, and a cohort of septic patients with elevated liver enzymes...
October 14, 2016: Medical Mycology: Official Publication of the International Society for Human and Animal Mycology
Thiago Alves da Costa, Rosária Di Gangi, Rodolfo Thomé, Marina Barreto Felisbino, Amanda Pires Bonfanti, Larissa Lumi Watanabe Ishikawa, Alexandrina Sartori, Eva Burger, Liana Verinaud
T cell maturation takes place within the thymus, a primary lymphoid organ that is commonly targeted during infections. Previous studies showed that acute infection with Paracoccidioides brasiliensis (Pb), the causative agent of paracoccidioidomycosis (PCM), promotes thymic atrophy that is associated with the presence of yeast cells in the organ. However, as human PCM is a chronic infection, it is imperative to investigate the consequences of Pb infection over the thymic structure and function in chronic infection...
2016: PloS One
José F Muñoz, Rhys A Farrer, Christopher A Desjardins, Juan E Gallo, Sean Sykes, Sharadha Sakthikumar, Elizabeth Misas, Emily A Whiston, Eduardo Bagagli, Celia M A Soares, Marcus de M Teixeira, John W Taylor, Oliver K Clay, Juan G McEwen, Christina A Cuomo
The Paracoccidioides genus includes two species of thermally dimorphic fungi that cause paracoccidioidomycosis, a neglected health-threatening human systemic mycosis endemic to Latin America. To examine the genome evolution and the diversity of Paracoccidioides spp., we conducted whole-genome sequencing of 31 isolates representing the phylogenetic, geographic, and ecological breadth of the genus. These samples included clinical, environmental and laboratory reference strains of the S1, PS2, PS3, and PS4 lineages of P...
September 2016: MSphere
Juan David Puerta-Arias, Paula Andrea Pino-Tamayo, Julián Camilo Arango, Ángel González
Chronic stages of paracoccidioidomycosis (PCM) are characterized by granulomatous lesions which promote the development of pulmonary fibrosis leading to the loss of respiratory function in 50% of patients; in addition, it has been observed that neutrophils predominate during these chronic stages of P. brasiliensis infection. The goal of this study was to evaluate the role of the neutrophil during the chronic stages of experimental pulmonary PCM and during the fibrosis development and tissue repair using a monoclonal specific to this phagocytic cell...
2016: PloS One
Lucas Nojosa Oliveira, Luciana Casaletti, Sônia Nair Báo, Clayton Luiz Borges, Patrícia de Sousa Lima, Célia Maria de Almeida Soares
Paracoccidioidomycosis is an endemic disease in Latin America, caused by thermo dimorphic fungi of the genus Paracoccidioides. Although previous proteome analyses of Paracoccidioides spp. have been carried out, the nuclear subproteome of this pathogen has not been described. In this way, we aimed to characterize the nuclear proteome of Paracoccidioides species, in the yeast form. For that, yeast cells were disrupted and submitted to cell fractionation. The purity of the nuclear fraction was confirmed by fluorescence and electron microscopy...
October 2016: Fungal Biology
Kristie D Goughenour, Chad A Rappleye
Dimorphic fungi cause several endemic mycoses which range from subclinical respiratory infections to life-threatening systemic disease. Pathogenic-phase cells of Histoplasma, Blastomyces, Paracoccidioides and Coccidioides escape elimination by the innate immune response with control ultimately requiring activation of cell-mediated immunity. Clinical management of disease relies primarily on antifungal compounds; however, dimorphic fungal pathogens create a number of challenges for antifungal drug therapy. In addition to the drug toxicity issues known for current antifungals, barriers to efficient drug treatment of dimorphic fungal infections include natural resistance to the echinocandins, residence of fungal cells within immune cells, the requirement for systemic delivery of drugs, prolonged treatment times, potential for latent infections, and lack of optimized standardized methodology for in vitro testing of drug susceptibilities...
September 19, 2016: Virulence
Paula Andrea Pino-Tamayo, Juan David Puerta-Arias, Damaris Lopera, Martha Eugenia Urán-Jiménez, Ángel González
Neutrophils predominate during the acute phase of the Paracoccidioides brasiliensis infection. Herein, we determined the role of the neutrophil during the early stages of experimental pulmonary paracoccidioidomycosis using a monoclonal antibody (mAb) specific for neutrophils. Male BALB/c mice were inoculated intranasally with 1.5 × 10(6) or 2 × 10(6) P. brasiliensis yeast cells. The mAb was administered 24 h before infection, followed by doses every 48 h until mice were sacrificed. Survival time was evaluated and mice were sacrificed at 48 h and 96 h after inoculation to assess cellularity, fungal load, cytokine/chemokine levels, and histopathological analysis...
2016: Mediators of Inflammation
Taise Natali Landgraf, Fabrício Freitas Fernandes, Gabriela Peron, Ademilson Panunto-Castelo
The lack of antifungals with low toxicity and short-term therapy for patients with paracoccidioidomycosis (PCM) led us to evaluate adjuvants in immunotherapeutic intervention. We have previously shown complete Freund's adjuvant (CFA) to be therapeutic on experimental PCM. Owing to CFA toxicity, here we tested adjuvants approved for clinical use or in preclinical phase in experimental mouse PCM. Of all, only monophosporyl lipid A (MPLA) demonstrates a beneficial effect, by reducing the fungal burden and increasing the concentrations of IFN-γ and TNF-α, which are immunoprotective in PCM...
September 17, 2016: Medical Mycology: Official Publication of the International Society for Human and Animal Mycology
Caroline Maria Marcos, Haroldo Cesar de Oliveira, Julhiany de Fátima da Silva, Patricia Akemi Assato, Daniella Sayuri Yamazaki, Rosângela Aparecida Moraes da Silva, Cláudia Tavares Santos, Norival Alves Santos-Filho, Deivys Leandro Portuondo, Maria José Soares Mendes-Giannini, Ana Marisa Fusco-Almeida
Paracoccidioides spp., which are temperature-dependent dimorphic fungi, are responsible for the most prevalent human systemic mycosis in Latin America, the paracoccidioidomycosis. The aim of this study was to characterise the involvement of elongation factor Tu (EF-Tu) in Paracoccidioides brasiliensis-host interaction. Adhesive properties were examined using recombinant PbEF-Tu proteins and the respective polyclonal anti-rPbEF-Tu antibody. Immunogold analysis demonstrated the surface location of EF-Tu in P...
November 2016: FEMS Yeast Research
Fabrício Freitas Fernandes, Leandro Licursi de Oliveira, Taise Natali Landgraf, Gabriela Peron, Marcelo Vieira Costa, Arlete A M Coelho-Castelo, Vânia L D Bonato, Maria-Cristina Roque-Barreira, Ademilson Panunto-Castelo
The genus Paracoccidioides comprises species of dimorphic fungi that cause paracoccidioidomycosis (PCM), a systemic disease prevalent in Latin America. Here, we investigated whether administration of native 60-kDa heat shock protein of P. brasiliensis (nPbHsp60) or its recombinant counterpart (rPbHsp60) affected the course of experimental PCM. Mice were subcutaneously injected with nPbHsp60 or rPbHsp60 emulsified in complete's Freund Adjuvant (CFA) at three weeks after intravenous injection of P. brasiliensis yeasts...
2016: PloS One
Fabiana Rocha-Silva, Luciana Inácia Gomes, Alfredo Miranda Góes, Cidiane Graciele-Melo, Rachel Basques Caligiorne
: Paracoccidioidomycosis (PCM) is a systemic mycosis caused by dimorphic fungi Paracoccidioides brasiliensis and P. lutzii. It is prevalent in Latin American, mainly in Brazil. Therefore, PCM has fundamental impact in the Brazilian global economy, especially in public health system, since it is affecting economical active population in different country regions. OBJECTIVE: The present study aimed to standardize the Real Time-Polymerase Chain Reaction (rt-PCR) for an efficient and safe PCM diagnosis by amplifying the recombinant protein PB27 gene, only expressed by specimens of Paracoccidioides genus...
September 5, 2016: Recent Patents on Endocrine, Metabolic & Immune Drug Discovery
Alison F A Chaves, Daniele G Castilho, Marina V Navarro, Ana K Oliveira, Solange M T Serrano, Alexandre K Tashima, Wagner L Batista
Paracoccidioides brasiliensis, a thermally dimorphic fungus, is the causative agent of paracoccidioidomycosis, a systemic mycosis that is widespread in Latin America. This fungus is a facultative intracellular pathogen able to survive and replicate inside non-activated macrophages. Therefore, the survival of P. brasiliensis inside the host depends on the ability to adapt to oxidative stress induced by immune cells, especially alveolar macrophages. For several years, reactive oxygen species (ROS) were only associated with pathological processes...
August 30, 2016: Microbes and Infection
Mariana Vieira Tomazett, Fabiana Fonseca Zanoelo, Elisa Flávia Cardoso Bailão, Alexandre Melo Bailão, Clayton Luiz Borges, Célia Maria de Almeida Soares
Carbonic anhydrases (CA) belong to the family of zinc metalloenzymes that catalyze the reversible hydration of carbon dioxide to bicarbonate. In the present work, we characterized the cDNAs of four Paracoccidioides CAs (CA1, CA2, CA3, and CA4). In the presence of CO2, there was not a significant increase in fungal ca1, ca2 and ca4 gene expression. The ca1 transcript was induced during the mycelium-to-yeast transition, while ca2 and ca4 gene expression was much higher in yeast cells, when compared to mycelium and mycelium-to-yeast transition...
July 2016: Genetics and Molecular Biology
Rosana Puccia, Milene Carmes Vallejo, Larissa V G Longo
Paracoccidioides brasiliensis and P. lutzii cause human paracoccidioidomycosis (PCM). They are dimorphic ascomycetes that grow as filaments at mild temperatures up to 28°C and as multibudding pathogenic yeast cells at 37°C. Components of the fungal cell wall have an important role in the interaction with the host because they compose the cell outermost layer. The Paracoccidioides cell wall is composed mainly of polysaccharides, but it also contains proportionally smaller rates of proteins, lipids, and melanin...
August 12, 2016: Current Protein & Peptide Science
Vanessa Noal, Suelen Santos, Karen Spadari Ferreira, Sandro Rogerio Almeida
: Paracoccidioidomycosis is a systemic mycosis endemic to Latin America. The infection is initiated by inhalation of conidia into the lung and may develop as localized or disseminated disease depending on the depression of cellular immunity. In the present study, we observed that intratracheal infection with P.b. caused the percentage of resident B-1 cells to decrease. Using xid mice reconstituted with B-1 cells, we observed that B-1 cells migrate to the spleen and stimulate increases in the regulatory T cell subpopulation in response to P...
August 10, 2016: Microbes and Infection
Leandro Nascimento da Silva Rodrigues, Wesley de Almeida Brito, Ana Flávia Alves Parente, Simone Schneider Weber, Alexandre Melo Bailão, Luciana Casaletti, Clayton Luiz Borges, Célia Maria de Almeida Soares
The ability to respond to stressful conditions is essential for most living organisms. In pathogenic organisms, this response is required for effective transition from a saprophytic lifestyle to the establishment of pathogenic interactions within a susceptible host. Hyperosmotic stress has been used as a model to study signal transduction and seems to cause many cellular adaptations, including the alteration of protein expression and cellular volume as well as size regulation. In this work, we evaluated the proteomic profile of Paracoccidioides lutzii Pb01 yeast cells during osmotic stress induced by potassium chloride...
October 2016: Fungal Genetics and Biology: FG & B
Mariana Vieira Tomazett, Fabiana Fonseca Zanoelo, Elisa Flávia Cardoso Bailão, Alexandre Melo Bailão, Clayton Luiz Borges, Célia Maria de Almeida Soares
Carbonic anhydrases (CA) belong to the family of zinc metalloenzymes that catalyze the reversible hydration of carbon dioxide to bicarbonate. In the present work, we characterized the cDNAs of four Paracoccidioides CAs (CA1, CA2, CA3, and CA4). In the presence of CO2, there was not a significant increase in fungal ca1, ca2 and ca4 gene expression. The ca1 transcript was induced during the mycelium-to-yeast transition, while ca2 and ca4 gene expression was much higher in yeast cells, when compared to mycelium and mycelium-to-yeast transition...
July 25, 2016: Genetics and Molecular Biology
Leonardo Nimrichter, Marcio M de Souza, Maurizio Del Poeta, Joshua D Nosanchuk, Luna Joffe, Patricia de M Tavares, Marcio L Rodrigues
Classic cell wall components of fungi comprise the polysaccharides glucans and chitin, in association with glycoproteins and pigments. During the last decade, however, system biology approaches clearly demonstrated that the composition of fungal cell walls include atypical molecules historically associated with intracellular or membrane locations. Elucidation of mechanisms by which many fungal molecules are exported to the extracellular space suggested that these atypical components are transitorily located to the cell wall...
2016: Frontiers in Microbiology
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