ABSTRACT
Cronobacter sakazakii is an opportunistic pathogen that has been associated with severe infection in neonates such as necrotizing enterocolitis (NEC), neonatal meningitis, and bacteremia. This pathogen can survive in a relatively dry environment, especially in powdered infant formula (PIF). Unfortunately, conventional drugs that were once effective against C. sakazakii are gradually losing their efficacy due to rising antibiotic resistance. In this study, a subtractive genomic approach was followed in order to identify potential therapeutic targets in the pathogen. The whole proteome of the pathogen was filtered through a step-by-step process, which involved removing paralogous proteins, human homologs, sequences that are less essential for survival, proteins with shared metabolic pathways, and proteins that are located in cells other than the cytoplasmic membrane. As a result, nine novel drug targets were identified. Further, the analysis also unveiled that the FDA-approved drug Terbinafine can be repurposed against the Glutathione/l-cysteine transport system ATP-binding/permease protein CydC of C. sakazakii. Moreover, molecular docking and dynamics studies of Terbinafine and CydC suggested that this drug can be used to treat C. sakazakii infection in neonates. However, for clinical purposes further in vitro and in vivo studies are necessary.
ABSTRACT
BACKGROUND: Xanthomonas oryzae pv. oryzae is a plant pathogen responsible for causing one of the most severe bacterial diseases in rice, known as bacterial leaf blight that poses a major threat to global rice production. Even though several experimental compounds and chemical agents have been tested against X. oryzae pv. oryzae, still no approved drug is available. In this study, a subtractive genomic approach was used to identify potential therapeutic targets and repurposible drug candidates that could control of bacterial leaf blight in rice plants. RESULTS: The entire proteome of the pathogen underwent an extensive filtering process which involved removal of the paralogous proteins, rice homologs, non-essential proteins. Out of the 4382 proteins present in Xoo proteome, five hub proteins such as dnaA, dnaN, recJ, ruvA, and recR were identified for the druggability analysis. This analysis led to the identification of dnaN-encoded Beta sliding clamp protein as a potential therapeutic target and one experimental drug named [(5R)-5-(2,3-dibromo-5-ethoxy-4hydroxybenzyl)-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid that can be repurposed against it. Molecular docking and 100 ns long molecular dynamics simulation suggested that the drug can form stable complexes with the target protein over time. CONCLUSION: Findings from our study indicated that the proposed drug showed potential effectiveness against bacterial leaf blight in rice caused by X. oryzae pv. oryzae. It is essential to keep in consideration that the procedure for developing novel drugs can be challenging and complicated. Even the most promising results from in silico studies should be validated through further in vitro and in vivo investigation before approval.
ABSTRACT
BACKGROUND: Gastric cancer, which is also known as stomach cancer, can be influenced by both germline and somatic mutations. Non-synonymous Single Nucleotide Polymorphisms (nsSNPs) in germline have long been reported to play a pivotal role in cancer progression. AIM: The aim of this study is to examine the nsSNP in GC-associated genes. The study also aims to develop a database with extensive information regarding the nsSNPs in the GC-associated genes and their impacts. METHODS AND RESULTS: A total of 34,588 nsSNPs from 1,493,460 SNPs of the 40 genes were extracted from the available SNP database. Drug binding and energy minimization were examined by molecular docking and YASARA. To validate the existence of the germline CDH1 gene mutation (rs34466743) in the isolated blood DNA of gastric cancer (GC) patients, polymerase chain reaction (PCR) and DNA sequencing were performed. According to the results of the gene network analysis, 17 genes may interact with other types of cancer. A total of 11,363 nsSNPs were detected within the 40 GC genes. Among these, 474 nsSNPs were predicted to be damaging and 40 to be the most damaging. The SNPs in domain regions were thought to be strong candidates that alter protein functions. Our findings proposed that most of the selected nsSNPs were within the domains or motif regions. Free Energy Deviation calculation of protein structure pointed toward noteworthy changes in the structure of each protein that can demolish its natural function. Subsequently, drug binding confirmed the structural variation and the ineffectiveness of the drug against the mutant model in individuals with these germline variants. Furthermore, in vitro analysis of the rs34466743 germline variant from the CDH1 gene confirmed the strength and robustness of the pipeline that could expand the somatic alteration for causing cancer. In addition, a comprehensive gastric cancer polymorphism database named "GasCanBase" was developed to make data available to researchers. CONCLUSION: The findings of this study and the "GasCanBase" database may greatly contribute to our understanding of molecular epidemiology and the development of precise therapeutics for gastric cancer. GasCanBase is available at: https://www.gascanbase.com/.
Subject(s)
Stomach Neoplasms , Humans , Stomach Neoplasms/genetics , Molecular Docking Simulation , Germ-Line Mutation , Polymerase Chain Reaction , Germ CellsABSTRACT
The objective this study was to assess the effect of gamma radiation and 2% potassium sorbate with low temperature (4 °C) for shrimp (Penaeus monodon) preservation. Fresh samples were prepared for treatment with gamma radiation at 1.0 and 1.5 kGy doses and potassium sorbate (2%) soaked for 30 s (PS 30 s) and 60 s (PS 60 s). Organoleptic score (OS), biochemical composition and microbiological analysis were performed to evaluate the shelf-life extension and quality changes during the storage periods. Data showed that combination treatment of gamma irradiation at 1.5 kGy with low temperature was the most effective in extending shelf-life of shrimp. The isolated bacteria associated with shrimp samples were identified through PCR technique. Antibiotic sensitivity test was examined using ten commonly used antibiotics against these pathogenic isolates. Gentamicin and Imipenem showed up to 50% resistance on Gram-positive (Bacillus cereus and Staphylococcus aureus). This study indicates that gamma irradiation treatment with low temperature was most effective way for shelf-life extension of shrimp which might reduce the wastage of this important nutritional source.
ABSTRACT
Coronavirus disease-19 (COVID-19) caused by SARS-CoV-2 has already killed more than one million people worldwide. Since novel coronavirus is a new virus, mining its genome sequence is of crucial importance for drug/vaccine(s) development. Whole genome sequencing is a helpful tool in identifying genetic changes that occur in a virus when it spreads through the population. In this study, we performed complete genome sequencing of SARS-CoV-2 to unveil the genomic variation and indel, if present. We discovered thirteen (13) mutations in Orf1ab, S and N gene where seven (7) of them turned out to be novel mutations from our sequenced isolate. Besides, we found one (1) insertion and seven (7) deletions from the indel analysis among the 323 Bangladeshi isolates. However, the indel did not show any effect on proteins. Our energy minimization analysis showed both stabilizing and destabilizing impact on viral proteins depending on the mutation. Interestingly, all the variants were located in the binding site of the proteins. Furthermore, drug binding analysis revealed marked difference in interacting residues in mutants when compared to the wild type. Our analysis also suggested that eleven (11) mutations could exert damaging effects on their corresponding protein structures.
