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.
