Low Concentrations of Hydrogen Peroxide or Nitrite Induced of Paracoccidioides brasiliensis Cell Proliferation in a Ras-Dependent Manner

Paracoccidioides brasiliensis, a causative agent of paracoccidioidomycosis (PCM), should be able to adapt to dramatic environmental changes inside the infected host after inhalation of air-borne conidia and transition to pathogenic yeasts. Proteins with antioxidant functions may protect fungal cells against reactive oxygen (ROS) and nitrogen (RNS) species generated by phagocytic cells, thus acting as potential virulence factors. Ras GTPases are involved in stress responses, cell morphology, and differentiation in a range of organisms. Ras, in its activated form, interacts with effector proteins and can initiate a kinase cascade. in lower eukaryotes, Byr2 kinase represents a Ras target. the present study investigated the role of Ras in P. brasiliensis after in vitro stimulus with ROS or RNS. We have demonstrated that low concentrations of H2O2 (0.1 mM) or NO2 (0.1-0.25 mu M) stimulated P. brasiliensis yeast cell proliferation and that was not observed when yeast cells were pre-incubated with farnesyltransferase inhibitor. We constructed an expression plasmid containing the Byr2 Ras-binding domain (RBD) fused with GST (RBD-Byr2-GST) to detect the Ras active form. After stimulation with low concentrations of H2O2 or NO2, the Ras active form was observed in fungal extracts. Besides, NO2 induced a rapid increase in S-nitrosylated Ras levels. This alternative posttranslational modification of Ras, probably in residue Cys123, would lead to an exchange of GDP for GTP and consequent GTPase activation in P. brasiliensis. in conclusion, low concentrations of H2O2 or NO2 stimulated P. brasiliensis proliferation through Ras activation.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenacao Aperfeicoamento de Pessoal de Nivel SuperiorUniversidade Federal de São Paulo, Dept Microbiol Imunol & Parasitol, São Paulo, BrazilUniversidade Federal de São Paulo, Ctr Terapia Celular & Mol CTCMol, Dept Bioquim Biol Mol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Ciencias Biol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Microbiol Imunol & Parasitol, São Paulo, BrazilUniversidade Federal de São Paulo, Ctr Terapia Celular & Mol CTCMol, Dept Bioquim Biol Mol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Ciencias Biol, São Paulo, BrazilFAPESP: 2011/14392-2CNPq: 477764/2009-6Web of Scienc

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Estudo Do Papel Da Aspartil Protease (Pbsap) Na Virulência Do Fungo Patogênico Paracoccidioides Brasiliensis

Paracoccidioidomycosis (Pcm) Is The Most Prevalent Deep Mycosis In Latin America And Is Caused By Fungi From The Paracoccidioides Genus. The Development Of The Disease Depends On Factors Associated With The Host Immune Response And The Infectious Agent Characteristics, Especially Virulence. Virulence Factors Are Important Fungal Characteristics That Support The Development Of Disease. Aspartyl Proteases (Saps) Are Virulence Factors In Many Human Fungal Pathogens That Play An Important Role In The Host Invasion Process. We Report Here That Immunization With Recombinant Sap From Paracoccidioides Brasiliensis (Rpbsap) Imparted A Protective Effect In An Experimental Pcm Model. The Rpbsap-Immunized Mice Had Decreased Fungal Loads, And Their Lung Parenchymas Were Notably Preserved. Therapeutic Treatment Against Model Pcm Using Pepstatin A, An Aspartyl Protease Inhibitor,Decreased Pulmonary Injury And Reduced Fungal Loads In The Lung. Additionally, We Observed That Pepstatin A Enhanced The Fungicidal And PhagocyticA Paracoccidioidomicose (Pcm) É Uma Micose Sistêmica Prevalente Nos Países Da América Latina E É Causada Por Fungos Do Gênero Paracoccidioides Spp. O Desenvolvimento Da Doença Depende De Fatores Associados À Resposta Imune Do Hospedeiro E Às Características Do Agente Infeccioso, Especialmente A Virulência. Aspartil Proteases (Saps) São Clássicos Fatores De Virulência Em Fungos Patogênicos E Desempenham Um Papel Importante No Processo De Invasão Ao Hospedeiro. O Presente Trabalho Teve Como Objetivo Investigar O Papel Da Aspartil Protease Na Virulência De P. Brasiliensis. Neste Trabalho A Proteína Recombinante Rpbsap Foi Produzida E Utilizada Para Imunizar Camundongos Balb/C, A Qual Foi Capaz De Desenvolver Resposta Protetora Em Camundongos Na Pcm Experimental. Estes Animais Apresentaram Diminuição Da Carga Fúngica No Pulmão, Altos Níveis De Ifn-" E Parênquima Pulomar Preservado. O Tratamento Terapêutico Contra A Pcm Experimental Utilizando A Pepstatina A, Um Inibidor Da Aspartil Protease, Apresentou ResultadosDados abertos - Sucupira - Teses e dissertações (2018

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

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.FAPESP (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo/Brazil)CNPq (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico/Brazil)Univ Fed Sao Paulo UNIFESP, Dept Microbiol Immunol & Parasitol, BR-04023062 Sao Paulo, BrazilUniv Fed Sao Paulo UNIFESP, ICAQF, Dept Pharmaceut Sci, Campus Diadema,Rua Sao Nicolau 210, BR-09913030 Diadema, BrazilUniv Fed Sao Paulo UNIFESP, Dept Microbiol Immunol & Parasitol, BR-04023062 Sao Paulo, BrazilUniv Fed Sao Paulo UNIFESP, ICAQF, Dept Pharmaceut Sci, Campus Diadema,Rua Sao Nicolau 210, BR-09913030 Diadema, BrazilFAPESP: 2014/13961-1FAPESP: 2014/08987-1FAPESP: 2017/04592-0CNPq: 478023/2013-8Web of Scienc

NEOTROPICAL ALIEN MAMMALS: a data set of occurrence and abundance of alien mammals in the Neotropics

Biological invasion is one of the main threats to native biodiversity. For a species to become invasive, it must be voluntarily or involuntarily introduced by humans into a nonnative habitat. Mammals were among first taxa to be introduced worldwide for game, meat, and labor, yet the number of species introduced in the Neotropics remains unknown. In this data set, we make available occurrence and abundance data on mammal species that (1) transposed a geographical barrier and (2) were voluntarily or involuntarily introduced by humans into the Neotropics. Our data set is composed of 73,738 historical and current georeferenced records on alien mammal species of which around 96% correspond to occurrence data on 77 species belonging to eight orders and 26 families. Data cover 26 continental countries in the Neotropics, ranging from Mexico and its frontier regions (southern Florida and coastal-central Florida in the southeast United States) to Argentina, Paraguay, Chile, and Uruguay, and the 13 countries of Caribbean islands. Our data set also includes neotropical species (e.g., Callithrix sp., Myocastor coypus, Nasua nasua) considered alien in particular areas of Neotropics. The most numerous species in terms of records are from Bos sp. (n = 37,782), Sus scrofa (n = 6,730), and Canis familiaris (n = 10,084); 17 species were represented by only one record (e.g., Syncerus caffer, Cervus timorensis, Cervus unicolor, Canis latrans). Primates have the highest number of species in the data set (n = 20 species), partly because of uncertainties regarding taxonomic identification of the genera Callithrix, which includes the species Callithrix aurita, Callithrix flaviceps, Callithrix geoffroyi, Callithrix jacchus, Callithrix kuhlii, Callithrix penicillata, and their hybrids. This unique data set will be a valuable source of information on invasion risk assessments, biodiversity redistribution and conservation-related research. There are no copyright restrictions. Please cite this data paper when using the data in publications. We also request that researchers and teachers inform us on how they are using the data