RESUMO
Piscirickettsia salmonis is one of the main pathogens causing considerable economic losses in salmonid farming. The DNA gyrase of several pathogenic bacteria has been the target of choice for antibiotic design and discovery for years, due to its key function during DNA replication. In this study, we carried out a combined in silico and in vitro approach to antibiotic discovery targeting the GyrA subunit of Piscirickettsia salmonis. The in silico results of this work showed that flumequine (-6.6 kcal/mol), finafloxacin (-7.2 kcal/mol), rosoxacin (-6.6 kcal/mol), elvitegravir (-6.4 kcal/mol), sarafloxacin (-8.3 kcal/mol), orbifloxacin (-7.9 kcal/mol), and sparfloxacin (-7.2 kcal/mol) are docked with good affinities in the DNA binding domain of the Piscirickettsia salmonis GyrA subunit. In the in vitro inhibition assay, it was observed that most of these molecules inhibit the growth of Piscirickettsia salmonis, except for elvitegravir. We believe that this methodology could help to significantly reduce the time and cost of antibiotic discovery trials to combat Piscirickettsia salmonis within the salmonid farming industry.
Assuntos
Doenças dos Peixes , Piscirickettsia , Animais , Antibacterianos/farmacologia , Piscirickettsia/genética , DNA Girase/genética , Doenças dos Peixes/tratamento farmacológico , Doenças dos Peixes/microbiologiaRESUMO
Voltage-gated sodium channel activity has long been associated with several diseases including epilepsy, chronic pain, cardiovascular diseases, cancers, immune system, neuromuscular and respiratory disorders. The strong participation of these channels in the development of diseases makes them excellent promising therapeutic targets. Voltage-gated Na+ channel blocking peptides come from a wide source of organisms such as venoms. However, the in vitro and in vivo identification and validation of these peptides are time-consuming and resource-intensive. In this work, we developed a bioinformatics tool called PEP-PREDNa + for the highly specific prediction of voltage-gated Na+ channel blocking peptides. PEP-PREDNa+ is based on the random forest algorithm, which presented excellent performance measures during the cross-validation (sensitivity = 0.81, accuracy = 0.83, precision = 0.85, F-score = 0.83, specificity = 0.86, and Matthew's correlation coefficient = 0.67) and testing (sensitivity = 0.88, accuracy = 0.92, precision = 0.96, F-score = 0.91, specificity = 0.96, and Matthew's correlation coefficient = 0.84) phases. The PEP-PREDNa + tool could be very useful in accelerating and reducing the costs of the discovery of new voltage-gated Na+ channel blocking peptides with therapeutic potential.
Assuntos
Ativação do Canal Iônico , Peptídeos , Aprendizado de Máquina , Peptídeos/químicaRESUMO
The regulation of sperm motility is controlled by several variables, including mainly ion concentrations. In fish, Ca2+ concentrations play an important role in the regulation of sperm motility, and several reports highlight the importance of certain Ca2+ channels in the regulation of this cell function. CatSper is a calcium channel scarcely studied in fish. In the species Salmo salar, it has been shown that it is key in the regulation of sperm motility. Taking into account the relevance of this channel in sperm activation in fish, in this study we evaluated the presence and probable functionality of this channel in the class Actinopterygii. For this purpose, a rational bioinformatic analysis was carried out, which had been previously validated using in vitro techniques by our group. The bioinformatic analysis of the present work revealed that the functionality of CatSper of the species of the class Actinopterygii could be exclusive to freshwater and anadromous fish species. The results of this study showed that only some anadromous and freshwater fish species contain 11 subunits of the CatSper channel, which are enough to trigger sperm motility. Consequently, this study provides new data for a better understanding of the sperm activation mechanism in fish.
Assuntos
Biologia Computacional , Motilidade dos Espermatozoides , Animais , Membrana Celular , Peixes , Água Doce , MasculinoRESUMO
Viral antigens are key in the development of vaccines that prevent or eradicate infections caused by these pathogens. Bioinformatics tools are modern alternatives that facilitate the discovery of viral antigens, reducing the costs of experimental assays. We developed a bioinformatics tool called VirVACPRED, which is highly efficient in predicting viral antigens. In this study, we obtained a model based on the gradient boosting classifier, which showed high performance during the training, leave-one-out cross-validation (accuracy = 0.7402, sensitivity = 0.7319, precision = 0.7503, F1 = 0.7251, kappa = 0.4774, Matthews correlation coefficient = 0.4981) and testing (accuracy = 0.8889, sensitivity = 1.0, precision = 0.8276, F1 = 0.9057, kappa = 0.7734, Matthews correlation coefficient = 0.7941). VirVACPRED is a robust tool that can be of great help in the search and proposal of new viral antigens, which can be considered in the development of future vaccines against infections caused by viruses.