title: Pangenome and immuno-proteomics analysis of Acinetobacter baumannii strains revealed the core peptide vaccine targets.
abstract: 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.
authors.affiliation: Atta-ur-Rahman School of Applied Biosciences (ASAB), National University of Sciences and Technology (NUST), H-12, Islamabad, Pakistan.
authors.forename: Afreenish
authors.initials: A
authors.lastname: Hassan
authors.affiliation: Atta-ur-Rahman School of Applied Biosciences (ASAB), National University of Sciences and Technology (NUST), H-12, Islamabad, Pakistan.
authors.forename: Anam
authors.initials: A
authors.lastname: Naz
authors.affiliation: Atta-ur-Rahman School of Applied Biosciences (ASAB), National University of Sciences and Technology (NUST), H-12, Islamabad, Pakistan.
authors.forename: Ayesha
authors.initials: A
authors.lastname: Obaid
authors.affiliation: Research Center for Modeling and Simulation (RCMS), National University of Sciences and Technology (NUST), H-12, Islamabad, Pakistan.
authors.forename: Rehan Zafar
authors.initials: RZ
authors.lastname: Paracha
authors.affiliation: Atta-ur-Rahman School of Applied Biosciences (ASAB), National University of Sciences and Technology (NUST), H-12, Islamabad, Pakistan.
authors.forename: Kanwal
authors.initials: K
authors.lastname: Naz
authors.affiliation: Atta-ur-Rahman School of Applied Biosciences (ASAB), National University of Sciences and Technology (NUST), H-12, Islamabad, Pakistan.
authors.forename: Faryal Mehwish
authors.initials: FM
authors.lastname: Awan
authors.affiliation: Institute of Molecular Biology and Biotechnology, Bahauddin Zakariya University, Multan, Pakistan.
authors.forename: Syed Aun
authors.initials: SA
authors.lastname: Muhmmad
authors.affiliation: Atta-ur-Rahman School of Applied Biosciences (ASAB), National University of Sciences and Technology (NUST), H-12, Islamabad, Pakistan.
authors.forename: Hussnain Ahmed
authors.initials: HA
authors.lastname: Janjua
authors.affiliation: Research Center for Modeling and Simulation (RCMS), National University of Sciences and Technology (NUST), H-12, Islamabad, Pakistan.|Department of Computer Science and Information Technology, Stratford University, Falls Church, VA, 22043, USA.
authors.forename: Jamil
authors.initials: J
authors.lastname: Ahmad
authors.affiliation: Atta-ur-Rahman School of Applied Biosciences (ASAB), National University of Sciences and Technology (NUST), H-12, Islamabad, Pakistan. amjaduni@gmail.com.
authors.forename: Amjad
authors.initials: A
authors.lastname: Ali
mesh_terms: D040981:Acinetobacter baumannii / Q000145:classification / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D000595:Amino Acid Sequence; D000942:Antigens, Bacterial / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D019295:Computational Biology / Q000379:methods; D018604:Epitope Mapping; D000939:Epitopes / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D019143:Evolution, Molecular; D016680:Genome, Bacterial; D023281:Genomics / Q000379:methods; D008958:Models, Molecular; D058977:Molecular Sequence Annotation; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D010802:Phylogeny; D011487:Protein Conformation; D025941:Protein Interaction Mapping; D060066:Protein Interaction Maps; D020543:Proteome; D040901:Proteomics / Q000379:methods; D022223:Vaccines, Subunit / Q000235:genetics / Q000276:immunology; D014774:Virulence / Q000235:genetics
chemical_list: D000942:Antigens, Bacterial; D000939:Epitopes; D010455:Peptides; D020543:Proteome; D022223:Vaccines, Subunit
keywords: A. baumannii; Core genome; Epitopes; Pan-genome; Vaccines