Comprehensive genome based analysis of Vibrio parahaemolyticus for identifying novel drug and vaccine molecules: Subtractive proteomics and vaccinomics approach.

Autor: Hasan M; Department of Pharmaceuticals and Industrial Biotechnology, Sylhet Agricultural University, Sylhet, Bangladesh., Azim KF; Department of Microbial Biotechnology, Sylhet Agricultural University, Sylhet, Bangladesh., Imran MAS; Department of Pharmaceuticals and Industrial Biotechnology, Sylhet Agricultural University, Sylhet, Bangladesh., Chowdhury IM; Department of Molecular Biology and Genetic Engineering, Sylhet Agricultural University, Sylhet, Bangladesh., Urme SRA; Department of Biochemistry and Chemistry, Sylhet Agricultural University, Sylhet, Bangladesh., Parvez MSA; Department of Genetic Engineering and Biotechnology, Shahjalal University of Science and Technology, Sylhet, Bangladesh., Uddin MB; Department of Medicine, Sylhet Agricultural University, Sylhet, Bangladesh., Ahmed SSU; Department of Epidemiology and Public Health, Sylhet Agricultural University, Sylhet, Bangladesh.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2020 Aug 19; Vol. 15 (8), pp. e0237181. Date of Electronic Publication: 2020 Aug 19 (Print Publication: 2020).
DOI: 10.1371/journal.pone.0237181
Abstrakt: Multidrug-resistant Vibrio parahaemolyticus has become a significant public health concern. The development of effective drugs and vaccines against Vibrio parahaemolyticus is the current research priority. Thus, we aimed to find out effective drug and vaccine targets using a comprehensive genome-based analysis. A total of 4822 proteins were screened from V. parahaemolyticus proteome. Among 16 novel cytoplasmic proteins, 'VIBPA Type II secretion system protein L' and 'VIBPA Putative fimbrial protein Z' were subjected to molecular docking with 350 human metabolites, which revealed that Eliglustat, Simvastatin and Hydroxocobalamin were the top drug molecules considering free binding energy. On the contrary, 'Sensor histidine protein kinase UhpB' and 'Flagellar hook-associated protein of 25 novel membrane proteins were subjected to T-cell and B-cell epitope prediction, antigenicity testing, transmembrane topology screening, allergenicity and toxicity assessment, population coverage analysis and molecular docking analysis to generate the most immunogenic epitopes. Three subunit vaccines were constructed by the combination of highly antigenic epitopes along with suitable adjuvant, PADRE sequence and linkers. The designed vaccine constructs (V1, V2, V3) were analyzed by their physiochemical properties and molecular docking with MHC molecules- results suggested that the V1 is superior. Besides, the binding affinity of human TLR-1/2 heterodimer and construct V1 could be biologically significant in the development of the vaccine repertoire. The vaccine-receptor complex exhibited deformability at a minimum level that also strengthened our prediction. The optimized codons of the designed construct was cloned into pET28a(+) vector of E. coli strain K12. However, the predicted drug molecules and vaccine constructs could be further studied using model animals to combat V. parahaemolyticus associated infections.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
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