Browsing by Author "Cosenza Contreras, Miguel de Jesus"

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    Shotgun proteomics of Strongyloides venezuelensis infective third stage larvae : insights into host-parasite interaction and novel targets for diagnostics.
    (2020) Fonseca, Priscilla Duarte Marques; Corral, Marcelo Andreetta; Cosenza Contreras, Miguel de Jesus; Meisel, Dirce Mary Correia Lima; Melo, Gessica Baptista de; Antunes, Milena Monteiro de Souza; Santo, Maria C. E.; Gryschek, Ronaldo Cesar Borges; Cruz, Julia Maria Costa; Borges, William de Castro; Paula, Fabiana Martins de
    Strongyloides venezuelensis is an important alternative source of antigen for the serologic diagnosis of human strongyloidiasis. Proteomics techniques applied to the analysis of the protein content of infective third stage larvae (iL3) of S. venezuelensis provide a powerful tool for the discovery of new candidates for immunodiagnosis. This study presents an overview of the protein iL3 S. venezuelensis focusing on the diagnosis of strongyloidiasis. A total of 877 proteins were identified by shotgun proteomics. Many of these proteins are involved in different cellular processes, metabolic as well as structural maintenance. Our results point to a catalog of possible diagnostic targets for human strongyloidiasis and highlight the need for evaluation of uncharacterized proteins, especially the proteins within the CAP domain, transthyretin, and BTPI inhibitor domains, as a repertoire as yet unexplored in the context of strongyloidiasis diagnostic markers. We believe that the protein profile presented in this shotgun analysis extends our understanding of the protein composition within the Strongyloides genus, opening up new perspectives for research on biomarkers that may help with the diagnosis of human strongyloidiasis. Data are available via ProteomeXchange with identifier PXD013703.
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    The golden mussel proteome and its response to niclosamide : uncovering rational targets for control or elimination.
    (2020) Sanson, Ananda Lima; Cosenza Contreras, Miguel de Jesus; Marco, Ricardo De; Neves, Leandro Xavier; Mattei, Bruno; Silva, Gustavo Gonçalves; Magalhães, Paulo Henrique Vieira; Andrade, Milton Hércules Guerra de; Borges, William de Castro
    The Asian invasive species Limnoperna fortunei (Dunker, 1857), known as the golden mussel, causes great economic and environmental damage due to its fixative capacity and accelerated proliferation. Molecular studies for the control of larval and adult forms are of great economic, scientific and technological interest. Here, we first report on the compositional analysis of the L. fortunei proteome obtained through shotgun analysis using LC-MS/ MS. Among those 2790 proteins identified, many of them related to secretory processes and membrane receptors. Our second approach consisted in exposing the mollusc to the molluscicide niclosamide to evaluate the induced proteomic alterations. Exposure to niclosamide at 0.25 mg/L for 24 h resulted in a pronounced differential abundance of proteins when compared to those obtained when exposure was reduced to 4 h at 2.3 mg/ L. In total, 342 proteins were found differentially expressed in the responsive individuals as revealed by labelfree quantitative proteomics. Regarding the affected cell processes were: cell division and differentiation, cytoskeletal organization and compartment acidification (upregulated), and energy metabolism (downregulated). Our findings constitute the first inventory of the expressed proteome of the golden mussel and have the potential to contribute with a more rational proposition of molecular targets for control and monitoring of this species. Significance: With the recent availability of transcriptomic and genomic data applied to L. fortunei the timing is right to interrogate its putative gene repertoire using proteomic techniques. These have the potential to validate the existence of the predicted genes, infer their relative abundance and quantify their levels as a response to environmental stressors or various agents. Here we provided an inventory of the golden mussel proteome and evaluated its response to the molluscicide niclosamide. The obtained results open new avenues for intervention aimed at its control or elimination, particularly by targeting the various cellular processes that were uncovered.
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    The schistosomiasis spleenOME : unveiling the proteomic landscape of splenomegaly using label-free mass spectrometry.
    (2019) Cosenza Contreras, Miguel de Jesus; Castro, Renata Alves de Oliveira e; Mattei, Bruno; Campos, Jonatan Marques; Silva, Gustavo Gonçalves; Paiva, Nívia Carolina Nogueira de; Soares, Rodrigo Dian de Oliveira Aguiar; Carneiro, Cláudia Martins; Afonso, Luís Carlos Crocco; Borges, William de Castro
    Schistosomiasis is a neglected parasitic disease that affects millions of people worldwide and is caused by helminth parasites from the genus Schistosoma. When caused by S. mansoni, it is associated with the development of a hepatosplenic disease caused by an intense immune response to the important antigenic contribution of adult worms and to the presence of eggs trapped in liver tissue. Although the importance of the spleen for the establishment of immune pathology is widely accepted, it has received little attention in terms of the molecular mechanisms operating in response to the infection. Here, we interrogated the spleen proteome using a label-free shotgun approach for the potential discovery of molecular mechanisms associated to the peak of the acute phase of inflammation and the development of splenomegaly in the murine model. Over fifteen hundred proteins were identified in both infected and control individuals and 325 of those proteins were differentially expressed. Two hundred and forty-two proteins were found upregulated in infected individuals while 83 were downregulated. Functional enrichment analyses for differentially expressed proteins showed that most of them were categorized within pathways of innate and adaptive immunity, DNA replication, vesicle transport and catabolic metabolism. There was an important contribution of granulocyte proteins and antigen processing and presentation pathways were augmented, with the increased expression of MHC class II molecules but the negative regulation of cysteine and serine proteases. Several proteins related to RNA processing were upregulated, including splicing factors. We also found indications of metabolic reprogramming in spleen cells with downregulation of proteins related to mitochondrial metabolism. Ex-vivo imunophenotyping of spleen cells allowed us to attribute the higher abundance of MHC II detected by mass spectrometry to increased number of macrophages (F4/80+/MHC II+ cells) in the infected condition. We believe these findings add novel insights for the understanding of the immune mechanisms associated with the establishment of schistosomiasis and the processes of immune modulation implied in the host-parasite interactions.
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    Using label-free shotgun proteomics and systems biology to explore the complex immune dynamic of splenomegaly during acute schistosomiasis mansoni.
    (2019) Cosenza Contreras, Miguel de Jesus; Borges, William de Castro; Magalhães, Lizandra Guidi; Vieira, Paula Melo de Abreu; Borges, William de Castro
    Schistosomiasis is a neglected tropical disease that affect millions of people worldwide and it is caused by the infection with parasites of the genus Schistosoma. When caused by S. mansoni, schistosomiasis is characterized by the formation of liver granuloma, due to the presence of eggs trapped in the tissue, and the concurrent development of liver fibrosis that could lead to life lasting chronic complications. In this context, the spleen has been demonstrated to be a very responsible organ, with splenomegaly being one of the major hallmarks of schistosomiasis. Nevertheless, it has received little attention in terms of which immune and molecular mechanisms could be governing this host-parasite interplay and the development of this condition. In this study, we used mass spectrometry-based shotgun proteomics combined with systems biology tools to explore the complex molecular dynamic in the spleen at the acute phase of inflammation in a mice model of infection by S. mansoni. More than fifty hundred proteins were identified in the spleen proteome, and 325 of them were differentially expressed between infected and control individuals. Functional enrichment analyses showed that most differentially expressed proteins were categorized within pathways of innate and adaptive immunity, DNA replication, vesicle transport and catabolic metabolism. There was a significant enrichment of pathways associated with antigen processing and presentation, with an increased expression of MHC class II proteins and the negative regulation of cysteine and serine proteases. Indications of metabolic reprogramming were also found, with the downregulation of a set of proteins related to mitochondrial metabolism. It was also possible to establish a link between the variation in protein expression in the spleens with variations in subpopulations of spleen cells as revealed by flow cytometry analyses. These suggested the increased proportion of MHC-II-presenting macrophages with the higher abundance of MHC-II proteins measured by mass spectrometry. With this, we presented the first proteomic shotgun analysis of the spleen during schistosomiasis, offering new insights on the understanding of immune mechanisms associated with the establishment of the disease and other processes of immune modulation related to the host-parasite interplay.