Although members of the Paracoccidioides complex are not obligate intracellular pathogens, they present the ability to survive and multiply inside epithelial cells and phagocytes of mammals, which may favor the spread of the fungus in host tissues. Macrophages resident in the lung are the first line of defense against paracoccidioidomycosis (PCM), presenting mechanisms to control the pathogen dissemination through the granuloma formation or eliminating the fungus through phagocytosis. Phagocytosis triggers an oxidative burst, in which there is an increase in the production of toxic elements, derived from oxygen and nitrogen. The interior of the phagolysosome is a harsh environment to the internalized pathogens, since in addition to the oxygen and nitrogen reactive species, microorganisms face nutrient shortages and proteases activity. Through the NanoUPLC-MSE technology, we analyzed the proteomic response of Paracoccidioides brasiliensis during the infection of alveolar macrophages primed or not by interferon gamma (IFN-γ). At 6 hs post-infection, only (IFN-γ)-primed macrophages were able to kill the fungus. We observed the regulation of amino acids degradation, tricarboxylic acid cycle, respiratory chain, ATP synthesis, glyoxylate cycle, as well as an increase in the expression of defense proteins related to oxidative stress, heat shock, and virulence factors under both conditions analyzed. However, some pathways described as essential for the survival of pathogens inside macrophages were observed only or with higher intensity in yeast cells recovered from non-primed macrophages, as phosphate pentoses pathway, methylcitrate cycle, synthesis of cell wall components, and mitochondrial activity. The data indicate that the intracellular environment of non-primed macrophages could be more permissive to the survival and multiplication of P. brasiliensis. The identification of key molecules for the establishment of infection can help the understanding of the nature of the parasite–host relationship and pathogenesis of PCM.
Paracoccidioidomycosis (PCM), a systemic mycosis with a high incidence in Latin America, is caused by thermodimorphic fungi of the Paracoccidioides genus. The contact with host occurs by the inhalation of conidia or mycelial propagules which once reaching the pulmonary alveoli differentiate into yeast cells. This transition process is vital in the pathogenesis of PCM allowing the fungus survival in the host. Thus, the present work performed a comparative proteome analysis of mycelia, mycelia-to-yeast transition, and yeast cells of Paracoccidioides brasiliensis . For that, tryptic peptides were labeled with iTRAQ and identified by LC–MS/MS and computational data analysis, which allowed the identification of 312 proteins differentially expressed in different morphological stages. Data showed that P. brasiliensis yeast cells preferentially employ aerobic beta-oxidation and the tricarboxylic acid cycle accompanied by oxidative phosphorylation for ATP production, in comparison to mycelia and the transition from mycelia-to-yeast cells. Furthermore, yeast cells show a metabolic reprogramming in amino acid metabolism and in the induction of virulence determinants and heat shock proteins allowing adaptation to environmental conditions during the increase of the temperature. In opposite of that, the alcoholic fermentation found to P. lutzii , at least under laboratory conditions, is strongly favored in mycelium compared to yeast cells. Thereby, the data strongly support substantial metabolic differences among members of the Paracoccidioides complex, when comparing the saprobiotic mycelia and the yeast parasitic phases.
The objective was to evaluate and show the main impacts of excessive corporal weight, related to the complexities and clinical outcomes, caused by SARS-CoV-2. This work is based in a systematic review of published works and driven by the question: “Which are the main questions about obesity as a risk factor related to the clinical complications of COVID and severe respiratory diseases?”, the researches were realized based on MEDLINE data, through the keywords available in DeCS/MeSH: Coronavírus/Coronavirus, Obesidade/ Obesity and SARS-Cov-2/Betacoronavirus, and then through pre-fixed criteria, were selected 13 articles to make part of the same research. The severity of the infection caused by SARS-CoV-2 increased with the CMI, in patients with overweight, the needs for intensive therapy and mechanical ventilation were about 50%. The overweight can act as a deregulator, harming the lymphoids and myeloides answers, which will disrupt the immunological system and extend the infections, contributing to a higher proliferation of viral infections, as occurs in the COVID-19 pandemics, besides, those individuals usually have some pre-existing metabolic and endocrine disturbances which can contribute to the use of the immune system, inflammatory and viral pathogens. The obesity and overweight are directly related with the intensification of patients symptoms with COVID-19, trough disturbances in the immune system, lack of respiratory capability and complacency of the respiratory system, and by the presence of associated diseases to that pathology.
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