Identification of putative vaccine candidates and drug targets using 238 complete genome sequences of Klebsiella pneumoniae

Abstract

Klebsiella pneumoniae is a medically important species of the Klebsiella genus that causes mainly nosocomial infections in hospitals and other healthcare settings. The availability of complete genomes of this species has provided an opportunity to gain a better understanding of the genomic epidemiology, phylogeny and guided the development of antimicrobial therapies to control this bacterial infection. In this study, genome-level analysis is carried out on a dataset comprising of 238 K. pneumoniae complete genomes retrieved from the NCBI Genbank. We aimed to improve our understanding of the genomic diversity in the species and to estimate the evolutionary relationships between the studied taxa. Pangenome analysis confirmed significantly high diversity in K. pneumoniae strains isolated from various sources (environmental and pathogenic) around the World. Further, we explored the core genome for identification of novel therapeutic alternatives against K. pneumoniae to control antimicrobial resistance and infection. A comprehensive in silico hierarchical work plan is followed involving pangenomics, reverse vaccinology and subtractive proteomics to identify the core antigenic vaccine candidates and drug targets. Through reverse vaccinology approach, a total of nine B-cell derived T-cell epitopes are screened in four prioritized antigens which were then linked together and adjuvant to construct a multi-epitope peptide vaccine. Molecular dynamics simulation was applied to the designed vaccine and subsequent molecular docking with Toll-like Receptors 2 and 4 confirmed its agonistic properties. Meanwhile, through subtractive proteomics approach, total of eight potential drug targets are prioritized from the core proteome, namely GlrR, NtrC, OmpR, ArcA, PhoB, CreB, Basu, and PhoP. The therapeutic targets are proposed for suitable experimental testing and may lead to the development of drugs and vaccine to tackle priority pathogen.