Background: One of the major challenges for leishmaniasis treatment is the emergence of parasites resistant to antimony. In order to study differentially expressed genes associated with drug resistance we performed a comparative... more
Background: One of the major challenges for leishmaniasis treatment is the emergence of parasites resistant to antimony. In order to study differentially expressed genes associated with drug resistance we performed a comparative transcriptomic analysis between wild-type and potassium antimonyl tartrate (SbIII)-resistant Leishmania infantum lines using high-throughput RNA sequencing.Methods: All the cDNA libraries were constructed from promastigote forms of each line, sequenced and analyzed using STAR for mapping the reads against the reference genome (L. infantum JPCM5) and DESeq2 for differential expression statistical analyses. All the genes were functionally annotated using sequence similarity search.Results: The analytical pipeline considering an adjusted p-value lower than 0.05 and fold change greater than 2.0 identified 933 transcripts differentially expressed (DE) between wild-type and SbIII-resistant L. infantum lines. Out of 933 DE transcripts, 504 presented functional anno...
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Many vaccine candidates against visceral leishmaniasis (VL) have been proposed; however, to date, none of them have been efficacious for the human or canine disease. On this basis, the design of leishmaniasis vaccines has been constantly... more
Many vaccine candidates against visceral leishmaniasis (VL) have been proposed; however, to date, none of them have been efficacious for the human or canine disease. On this basis, the design of leishmaniasis vaccines has been constantly changing, and the use of approaches to select specific epitopes seems to be crucial in this scenario. The ability to predict T cell-specific epitopes makes immunoinformatics an even more necessary approach, as in VL an efficient immune response against the parasite is triggered by T lymphocytes in response to Leishmania spp. immunogenic antigens. Moreover, the success of vaccines depends on the capacity to generate long-lasting memory and polyfunctional cells that are able to eliminate the parasite. In this sense, our study used a combination of different approaches to develop potential chimera candidate vaccines against VL. The first point was to identify the most immunogenic epitopes of Leishmania infantum proteins and construct chimeras composed ...
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Reverse vaccinology or immunoinformatics is a computational methodology which integrates data from in silico epitope prediction, associated to other important information as, for example, the predicted subcellular location of the proteins... more
Reverse vaccinology or immunoinformatics is a computational methodology which integrates data from in silico epitope prediction, associated to other important information as, for example, the predicted subcellular location of the proteins used in the design of the context of vaccine development. This approach has the potential to search for new targets for vaccine development in the predicted proteome of pathogenic organisms. To date, there is no effective vaccine employed in vaccination campaigns against visceral leishmaniasis (VL). For the first time, herein, an in silico, in vitro, and in vivo peptide screening was performed, and immunogenic peptides were selected to constitute VL peptide-based vaccines. Firstly, the screening of in silico potential peptides using dogs naturally infected by L. infantum was conducted and the peptides with the best performance were selected. The mentioned peptides were used to compose Cockt-1 (cocktail 1) and Cockt-2 (cocktail 2) in combination wit...
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Due to an increase in the incidence of leishmaniases worldwide, the development of new strategies such as prophylactic vaccines to prevent infection and decrease the disease have become a high priority. Classic vaccines against... more
Due to an increase in the incidence of leishmaniases worldwide, the development of new strategies such as prophylactic vaccines to prevent infection and decrease the disease have become a high priority. Classic vaccines against leishmaniases were based on live or attenuated parasites or their subunits. Nevertheless, the use of whole parasite or their subunits for vaccine production has numerous disadvantages. Therefore, the use of peptides to design more specific vaccines against leishmaniases seems promising. Moreover, peptides have several benefits in comparison with other kinds of antigens, for instance, good stability, absence of potentially damaging materials, antigen low complexity, and low-cost to scale up. By contrast, peptides are poor immunogenic alone, and they need to be delivered correctly. In this context, several approaches described in this review are useful to solve these drawbacks. Approaches, such as, peptides in combination with potent adjuvants, cellular vaccina...
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In order to effectively control and monitor schistosomiasis, new diagnostic methods are essential. Taking advantage of computational approaches provided by immunoinformatics and considering the availability of Schistosoma mansoni... more
In order to effectively control and monitor schistosomiasis, new diagnostic methods are essential. Taking advantage of computational approaches provided by immunoinformatics and considering the availability of Schistosoma mansoni predicted proteome information, candidate antigens of schistosomiasis were selected and used in immunodiagnosis tests based on Enzime-linked Immunosorbent Assay (ELISA). The computational selection strategy was based on signal peptide prediction; low similarity to human proteins; B- and T-cell epitope prediction; location and expression in different parasite life stages within definitive host. Results of the above-mentioned analysis were parsed to extract meaningful biological information and loaded into a relational database developed to integrate them. In the end, seven proteins were selected and one B-cell linear epitope from each one of them was selected using B-cell epitope score and the presence of intrinsically disordered regions (IDRs). These predic...
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Antioxidant defense in Trypanosomatids has been indicated as a potential target for chemotherapy. Tryparedoxin peroxidase (TXNPx) participates in this defense by metabolizing hydrogen peroxide to water molecules. In this work, genes... more
Antioxidant defense in Trypanosomatids has been indicated as a potential target for chemotherapy. Tryparedoxin peroxidase (TXNPx) participates in this defense by metabolizing hydrogen peroxide to water molecules. In this work, genes encoding both cytosolic (cTcTXNPx) and mitochondrial (mTcTXNPx) TXNPx were characterized in 15 benznidazole-susceptible and resistant Trypanosoma cruzi strains. Northern blot and real-time RT-PCR analyses revealed that the levels of cTcTXNPx and mTcTXNPx mRNA were two-fold higher in the in-vitro-induced resistant 17 LER T. cruzi population than its drug-susceptible counterpart 17 WTS. The mRNA levels for both genes were similar among the other T. cruzi samples studied. No amplification of these genes was observed in the parasite genome. In silico analyses indicated that cTcTXNPx and mTcTXNPx genes present eight and two copies, respectively, dispersed in the parasite genome. By western blot analysis, anti-cTcTXNPx and anti-mTcTXNPx polyclonal antibodies recognized a 23- and 25-kDa peptide, respectively, in all T. cruzi samples analyzed. The expression levels of these native proteins were similar for all samples except 17 LER, which displayed two-fold greater expression. In addition, the oxidized mTcTXNPx protein (50 kDa) demonstrated 5.5-fold greater expression in the 17 LER population than 17 WTS. Our findings demonstrate increased expression of the cytosolic and mitochondrial TcTXNPx in the T. cruzi population with in-vitro-induced resistance to benznidazole.
Research Interests: Microbiology, Parasitology, Computational Biology, Medical Microbiology, Mitochondria, and 15 morePeroxidase, Humans, Parasite, Animals, Drug Resistance, Hydrogen Peroxide, Molecular Characterization, Trypanosoma Cruzi, Peroxidases, Veterinary Sciences, Trypanocidal Agents, Protozoan Proteins, In Silico, Induced Resistance, and reverse transcriptase polymerase chain reaction
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Research Interests: Comparative Genomics, Sequence Analysis, Gene Prediction, Biological Sciences, Molecular, and 10 moreAnimals, Protein Sequence Analysis, Genome sequence, Drug Targeting, Leishmania Major, Molecular Sequence Data, Sequence homology, conserved sequence , Medical and Health Sciences, and Leishmania braziliensis
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Research Interests: Bioinformatics, Evolutionary Biology, Informatics, Genomics, Computational Biology, and 15 moreBiotechnology, Cancer, Biomarkers, Biology, Biomedical informatics, Medicine, Bioscience, Evolutionary Bioinformatics, Microarray, Clinical Medicine, Biological, Genetic modification, Evidence Based, Biochemistry and cell biology, and ENVIRONMENTAL SCIENCE AND MANAGEMENT
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Research Interests: Genomics, Molecular Evolution, Comparative Genomics, Leishmania, Biological Sciences, and 15 moreLeishmaniasis, Humans, Animals, Visceral Leishmaniasis, Genome, Spectrum, Host Pathogen Interaction, Cutaneous Leishmaniasis, Leishmania infantum, Amino Acid Sequence, Human Disease, Leishmania Major, Molecular Sequence Data, Medical and Health Sciences, and Leishmania braziliensis
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Background Malaria has a devastating impact on worldwide public health in many tropical areas. Studies on vector immunity are important for the overall understanding of the parasite-vector interaction and for the design of novel... more
Background Malaria has a devastating impact on worldwide public health in many tropical areas. Studies on vector immunity are important for the overall understanding of the parasite-vector interaction and for the design of novel strategies to control malaria. A member of the fibrinogen-related protein family, fbn9, has been well studied in Anopheles gambiae and has been shown to be an important component of the mosquito immune system. However, little is known about this gene in neotropical anopheline species. Methods This article describes the identification and characterization of the fbn9 gene partial sequences from four species of neotropical anopheline primary and secondary vectors: Anopheles darlingi, Anopheles nuneztovari, Anopheles aquasalis, and Anopheles albitarsis (namely Anopheles marajoara). Degenerate primers were designed based on comparative analysis of publicly available Aedes aegypti and An. gambiae gene sequences and used to clone putative homologs in the neotropic...
Research Interests: Medical Microbiology, Malaria, Brazil, Aedes aegypti, Fibrinogen, and 15 moreAnopheles, Animals, Molecular Diversity, Comparative Analysis, Anopheles gambiae, Immune system, Control Strategy, Degeneration, Insect Immunity, Amino Acid Sequence, Base Sequence, Immunoglobulins, Nucleotides, Insect Vectors, and Nucleotide sequence
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Research Interests: Microbiology, Zoology, Polymorphism, Leishmania, Sequence alignment, and 15 moreParasite, Animals, Genome Analysis, Genome, Molecular cloning, Trypanosoma Cruzi, Trypanosoma brucei, Retrotransposons, For, Veterinary Sciences, Base Sequence, Leishmania Major, Nucleotides, DNA sequence, and Molecular Sequence Data
Leishmania species cause a spectrum of human diseases in tropical and subtropical regions of the world. We have sequenced the 36 chromosomes of the 32.8-megabase haploid genome of Leishmania major (Friedlin strain) and predict 911 RNA... more
Leishmania species cause a spectrum of human diseases in tropical and subtropical regions of the world. We have sequenced the 36 chromosomes of the 32.8-megabase haploid genome of Leishmania major (Friedlin strain) and predict 911 RNA genes, 39 pseudogenes, and 8272 protein-coding genes, of which 36% can be ascribed a putative function. These include genes involved in host-pathogen interactions, such as proteolytic enzymes, and extensive machinery for synthesis of complex surface glycoconjugates. The organization of protein-coding genes into long, strand-specific, polycistronic clusters and lack of general transcription factors in the L. major, Trypanosoma brucei, and Trypanosoma cruzi (Tritryp) genomes suggest that the mechanisms regulating RNA polymerase II-directed transcription are distinct from those operating in other eukaryotes, although the trypanosomatids appear capable of chromatin remodeling. Abundant RNA-binding proteins are encoded in the Tritryp genomes, consistent wit...
Research Interests: Science, Membrane Proteins, Multidisciplinary, Regulation of Gene Expression, Animals, and 15 moreChromatin remodeling, Lipid metabolism, Transcription Factor, Chromatin, Spectrum, Host Pathogen Interaction, Trypanosoma brucei, Cutaneous Leishmaniasis, Protozoan Proteins, Human Disease, Leishmania Major, Protein Biosynthesis, Gene Expression Regulation, Glycoconjugates, and Molecular Sequence Data
The sciarid DNA puff C4 BhC4-1 gene is amplified and transcribed in salivary glands at the end of the larval stage. In transgenic Drosophila, the BhC4-1 promoter drives transcription in prepupal salivary glands and in the ring gland of... more
The sciarid DNA puff C4 BhC4-1 gene is amplified and transcribed in salivary glands at the end of the larval stage. In transgenic Drosophila, the BhC4-1 promoter drives transcription in prepupal salivary glands and in the ring gland of late embryos. A bioinformatics analysis has identified 162 sequences similar to distinct regions of the BhC4-1 proximal promoter, which are predominantly located either in 5' or 3' regions or introns in the Drosophila melanogaster genome. A significant number of the identified sequences are found in the regulatory regions of Drosophila genes that are expressed in the salivary gland. Functional assays in Drosophila reveal that the BhC4-1 proximal promoter contains both a 129 bp (-186/-58) salivary gland enhancer and a 67 bp (-253/-187) ring gland enhancer that drive tissue specific patterns of developmentally regulated gene expression, irrespective of their orientation.
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Research Interests: Genetics, Algorithms, Computational Biology, Computer Networks, Biotechnology, and 15 moreCell Signaling, DNA repair, Biological Sciences, DNA, Computer Simulation, Animals, Cellular Networks, Genome, Enzyme, Gene fusion, Amino Acid Sequence, Enzymatic Activity, Experimental Method, Biochemistry and cell biology, and binding sites
Parasites of the genus Leishmania are the causative agents of a range of clinical manifestations collectively known as Leishmaniasis, a disease that affects 12 million people worldwide. With the aim of identifying potential secreted... more
Parasites of the genus Leishmania are the causative agents of a range of clinical manifestations collectively known as Leishmaniasis, a disease that affects 12 million people worldwide. With the aim of identifying potential secreted protein targets for further characterization, we have applied two-dimensional gel electrophoresis and mass spectrometry methods to study the soluble protein content of the microsomal fraction from two Leishmania species, Leishmania L. major and L. L. amazonensis. MALDI-TOF peptide mass fingerprint analysis of 33 protein spots from L. L. amazonensis and 41 protein spots from L. L. major identified 14 proteins from each sample could be unambiguously assigned. These proteins include the nucleotide diphosphate kinase (NDKb), a calpain-like protease, a tryparedoxin peroxidase (TXNPx) and a small GTP-binding Rab1-protein, all of which have a potential functional involvement with secretion pathways and/or environmental responses of the parasite. These results complement ongoing genomic studies in Leishmania, and are relevant to further understanding of host/parasite interactions.
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Background Epitope prediction using computational methods represents one of the most promising approaches to vaccine development. Reduction of time, cost, and the availability of completely sequenced genomes are key points and highly... more
Background Epitope prediction using computational methods represents one of the most promising approaches to vaccine development. Reduction of time, cost, and the availability of completely sequenced genomes are key points and highly motivating regarding the use of reverse vaccinology. Parasites of genus Leishmania are widely spread and they are the etiologic agents of leishmaniasis. Currently, there is no efficient vaccine against this pathogen and the drug treatment is highly toxic. The lack of sufficiently large datasets of experimentally validated parasites epitopes represents a serious limitation, especially for trypanomatids genomes. In this work we highlight the predictive performances of several algorithms that were evaluated through the development of a MySQL database built with the purpose of: a) evaluating individual algorithms prediction performances and their combination for CD8+ T cell epitopes, B-cell epitopes and subcellular localization by means of AUC (Area Under C...
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Research Interests: Bacteriology, Manganese, Biological Sciences, Functional data analysis, Humans, and 15 moreChild, Nitric oxide, Female, Iron, Genome Annotation, Gene Regulatory Networks, Environmental Conditions, Genome sequence, Base Sequence, Lymph Node, Bacterial Adhesion, Caseous Lymphadenitis, Corynebacterium Pseudotuberculosis, Functional Annotation, and Medical and Health Sciences
Recently a number of computational approaches have been developed for the prediction of protein���protein interactions. Complete genome sequencing projects have provided the vast amount of information needed for these analyses. These... more
Recently a number of computational approaches have been developed for the prediction of protein���protein interactions. Complete genome sequencing projects have provided the vast amount of information needed for these analyses. These methods utilize the structural, genomic, and biological context of proteins and genes in complete genomes to predict protein interaction networks and functional linkages between proteins. Given that experimental techniques remain expensive, time-consuming, and labor-intensive, these ...