The emergence of novel pathogenic strains with increased antibacterial resistance patterns poses a significant threat to the management of infectious diseases. In this study, we aimed at utilizing the subtractive genomic approach to identify novel drug targets against Salmonella enterica subsp. enterica serovar Poona strain ATCC BAA-1673. We employed in silico bioinformatics tools to subtract the strain-specific paralogous and host-specific homologous sequences from the bacterial proteome. The sorted proteome was further refined to identify the essential genes in the pathogenic bacterium using the database of essential genes (DEG). We carried out metabolic pathway and subcellular location analysis of the essential proteins of the pathogen to elucidate the involvement of these proteins in important cellular processes. We found 52 unique essential proteins in the target proteome that could be utilized as novel targets to design newer drugs. Further, we investigated these proteins in the DrugBank databases and 11 of the unique essential proteins showed druggability according to the FDA approved drug bank databases with diverse broad-spectrum property. Molecular docking analyses of the novel druggable targets with the drugs were carried out by AutoDock Vina option based on scoring functions. The results showed promising candidates for novel drugs against Salmonella infections.
Oxidative stress is considered a central factor in endothelial dysfunction and plaque formation in coronary heart disease (CHD) patients. In this crosssectional study, the stress-induced protein and lipid oxidation and production of signaling molecule, nitric oxide has been investigated in CHD patients in Bangladesh. A total of 140 participants were enrolled of which 70 were CHD patients, and the remaining 70 were control subjects having no cardiovascular disease. The diagnosis of CHD was made by expert physicians through characteristic electrocardiogram and troponin changes. The protein carbonyls and thiobarbituric acid reactive substances (TBARS) levels in plasma of both groups were measured by spectrophotometric methods. The plasma nitric oxide levels were measured by reaction with Griess reagent. Statistical non-parametric tests and t-tests were used to analyze the results between the CHD patients and controls. In the patients, the mean protein carbonyls and TBARS, two important markers of oxidative stress, were 2.87 ± 0.97 nmol/mg and 6.92 ± 3.56 nmol/mL, respectively, which were significantly higher than in the control subjects, 1.71 ± 0.82 nmol/mg and 3.15 ± 1.42 nmol/mL, respectively. Assessment of the cardiovascular signaling molecule nitric oxide showed significantly lower value in the CHD patients (6.29 ± 4.78 µM) compared to the controls (10.75 ± 6.03 µM). There was a significant negative correlation between plasma TBARS and total plasma protein, and a weak negative correlation between TBARS and nitric oxide levels in the CHD patients. Evaluation of the smoking habit strongly suggested that smoking was a risk factor for the development of CHD among the Bangladeshi population. These results provide an overview of oxidative stress-mediated damages on proteins, lipids and effects on signaling molecule nitric oxide in CHD patients.
Congenital heart disease (CHD) is the leading cause of birth defect-related death in infants and is a global pediatric health concern. While the genetic causes of CHD
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