Acinetobacter baumannii has emerged as a significant nosocomial pathogen during the last few years, exhibiting resistance to almost all major classes of antibiotics. Alternative treatment options such as vaccines tend to be most promising and cost effective approaches against this resistant pathogen. In the current study, we have explored the pan-genome of A. baumannii followed by immune-proteomics and reverse vaccinology approaches to identify potential core vaccine targets. The pan-genome of all available A. baumannii strains (30 complete genomes) is estimated to contain 7,606 gene families and the core genome consists of 2,445 gene families (~32 % of the pan-genome). Phylogenetic tree, comparative genomic and proteomic analysis revealed both intra- and inter genomic similarities and evolutionary relationships. Among the conserved core genome, thirteen proteins, including P pilus assembly protein, pili assembly chaperone, AdeK, PonA, OmpA, general secretion pathway protein D, FhuE receptor, Type VI secretion system OmpA/MotB, TonB dependent siderophore receptor, general secretion pathway protein D, outer membrane protein, peptidoglycan associated lipoprotein and peptidyl-prolyl cis-trans isomerase are identified as highly antigenic. Epitope mapping of the target proteins revealed the presence of antigenic surface exposed 9-mer T-cell epitopes. Protein-protein interaction and functional annotation have shown their involvement in significant biological and molecular processes. The pipeline is validated by predicting already known immunogenic targets against Gram negative pathogen Helicobacter pylori as a positive control. The study, based upon combinatorial approach of pan-genomics, core genomics, proteomics and reverse vaccinology led us to find out potential vaccine candidates against A. baumannii. The comprehensive analysis of all the completely sequenced genomes revealed thirteen putative antigens which could elicit substantial immune response. The integration of computational vaccinology strategies would facilitate in tackling the rapid dissemination of resistant A.baumannii strains. The scarcity of effective antibiotics and the global expansion of sequencing data making this approach desirable in the development of effective vaccines against A. baumannii and other bacterial pathogens.
A series of six novel benzimidazole-pyrazole hybrid molecules was synthesized and characterized using elemental analysis (CHN) and spectroscopic methods (1HNMR, FT-IR). All the synthesized compounds were evaluated for their in vivo anti ulcerogenic activity using Albino rats (weighing 180–220 g). The interactions between the compounds and active site residues of H+/K+ ATPase were investigated by molecular docking studies using autodock vina 4.0. SCH28080 was used to validate the docking results. Also the drug likeliness of these compounds was predicted using Molinspiration server in light of Lipinski’s rule of five. All the six synthesized compounds exhibited higher anti-ulcer activity as compared to omeprazole. These novel hybrid compounds showed comparable anti-ulcer potential of 72–83% at dose level of 500 µg/kg, whereas omeprazole showed 83% anti-ulcer activity at dose level of 30 mg/kg. The results clearly indicate that these novel benzimidazole-pyrazole hybrids can present a new class of potential anti ulcer agents and can serve as new anti-ulcer drugs after further investigation. Graphical abstract An overveiw of synthesis, in silico and in vivo antiulcer screening of benzimidazole pyrazole hybrids
1 August 2015 in Journal of Microbiological Methods
Chemotherapy resistance and peculiar tumor microenvironment, which diminish or mitigate the effects of therapies, make pancreatic cancer one of the deadliest malignancies to manage and treat. Advanced immunotherapies are under consideration intending to ameliorate the overall patient survival rate in pancreatic cancer. Oncolytic viruses therapy is a new type of immunotherapy in which a virus after infecting and lysis the cancer cell induces/activates patients’ immune response by releasing tumor antigen in the blood. The current review covers the pathways and molecular ablation that take place in pancreatic cancer cells. It also unfolds the extensive preclinical and clinical trial studies of oncolytic viruses performed and/or undergoing to design an efficacious therapy against pancreatic cancer.
1 November 2017 in Enzyme and Microbial Technology