Pangenome and immuno-proteomics analysis of Acinetobacter baumannii strains revealed the core peptide vaccine targets

Abstract

BackgroundAcinetobacter 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.ResultsThe 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.ConclusionThe 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-2951-4) contains supplementary material, which is available to authorized users.

Immuno-informatics Characterization SARS-CoV-2 Spike Glycoprotein for Prioritization of Epitope based Multivalent Peptide Vaccine

“…Epitopes with lowest percentile score were considered only as high affinity binders. The selected epitopes were then used in MHCPred 2.0 [42] to decipher their binding affinity potential for predominant HLA II DRB*0101 and only those with IC50 value < 100 nM were categorized as excellent DRB*0101 binders [43]. VirulentPred [44] was employed next to reveal virulent nature of the epitopes setting the cut-off to 0.5.…”

Physiology and Pathology of Multidrug-Resistant Bacteria: Antibodies- and Vaccines-Based Pathogen-Specific Targeting

“…It is now clear that multivalent antigens should be more potent in eliciting immune responses against bacteria. Combination of pan-genomics, proteomics, and reverse vaccinology analysis of bacteria revealed a list of conserved antigens as potential vaccine or antibody targets and some of these antigens are already known as virulence factors of related bacteria [186,187]. These bioinformatics-based "omics" analysis will undoubtedly facilitate efective vaccine and antibody target identiication and development.…”

Immuno-informatics driven proteome-wide investigation revealed novel peptide-based vaccine targets against emerging multiple drug resistant Providencia stuartii

“…Essential proteins were targeted as they play a significant role in pathogen's survival and any lethal mutation in these can result in the arrest of cell growth [22]. Surfaceexposed (exo-proteome) or secreted proteins (secretome) are suitable vaccine targets due to their frequent contact with the extracellular environment [23]; [39]. In addition, they serve as virulence factors and increase the pathogen's ability to adhere, invade, survive, and proliferate within the host cells [22]; [25].…”

“…The availability of genomic information allows the identification of suitable vaccine proteins in silico without the need to cultivate the pathogen. A proteome based approach for screening virulent antigens, Reverse Vaccinology (RV), has received more attention in recent years and has been used for the identification of vaccine proteins against different pathogens [21,22,23,24,25]. The RV approach was first applied to the bacterial pathogen Meningococcus B (MenB) [26], where RV played a significant role in screening for an antigen with the broadest bactericidal activity and ultimately resolved the long journey of MenB vaccine development [25]; [27].…”

“…Protein-protein interactions were explored for their cellular interacting network to understand the impact of protein inhibition on overall survival of the pathogen. In the epitope mapping phase, B-cell derived T-cell peptides for the proteins were predicted [22,23,24,25] and docked into the binding cavity of DRB1*0101 allele to identify their binding mode and interactions [25].…”