title: Antibiotic Resistance Determinant-Focused Acinetobacter baumannii Vaccine Designed Using Reverse Vaccinology.
abstract: As one of the most influential and troublesome human pathogens,Acinetobacter baumannii(A. baumannii) has emerged with many multidrug-resistant strains. After collecting 33 completeA. baumanniigenomes and 84 representative antibiotic resistance determinants, we used the Vaxign reverse vaccinology approach to predict classical type vaccine candidates againstA. baumanniiinfections and new type vaccine candidates against antibiotic resistance. Our genome analysis identified 35 outer membrane or extracellular adhesins that are conserved among all 33 genomes, have no human protein homology, and have less than 2 transmembrane helices. These 35 antigens include 11 TonB dependent receptors, 8 porins, 7 efflux pump proteins, and 2 fimbrial proteins (FilF and CAM87009.1). CAM86003.1 was predicted to be an adhesin outer membrane protein absent from 3 antibiotic-sensitive strains and conserved in 21 antibiotic-resistant strains. Feasible anti-resistance vaccine candidates also include one extracellular protein (QnrA), 3 RND type outer membrane efflux pump proteins, and 3 CTX-M type β-lactamases. Among 39 β-lactamases,A. baumanniiCTX-M-2, -5, and -43 enzymes are predicted as adhesins and better vaccine candidates than other β-lactamases to induce preventive immunity and enhance antibiotic treatments. This report represents the first reverse vaccinology study to systematically predict vaccine antigen candidates against antibiotic resistance for a microbial pathogen.
authors.affiliation: Department of Pathogenobiology, College of Basic Medical Science, Jilin University, Changchun 130021, China. nich@jlu.edu.cn.|Unit for Laboratory Animal Medicine, Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI 48109, USA. nich@jlu.edu.cn.
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Ni
authors.affiliation: Department of Neurosurgery, The Second Hospital of Jilin University, Changchun 130041, China. drchenyan@jlu.edu.cn.
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Unit for Laboratory Animal Medicine, Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI 48109, USA. edong@umich.edu.|Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA. edong@umich.edu.
authors.forename: Edison
authors.initials: E
authors.lastname: Ong
authors.affiliation: Unit for Laboratory Animal Medicine, Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI 48109, USA. yongqunh@med.umich.edu.|Center of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA. yongqunh@med.umich.edu.
authors.forename: Yongqun
authors.initials: Y
authors.lastname: He
mesh_terms: D000151:Acinetobacter Infections / Q000276:immunology / Q000517:prevention & control; D040981:Acinetobacter baumannii / Q000187:drug effects* / Q000235:genetics / Q000276:immunology*; D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001428:Bacterial Vaccines / Q000276:immunology*; D019295:Computational Biology / Q000379:methods; D017124:Conserved Sequence; D024881:Drug Resistance, Bacterial / Q000276:immunology*; D000939:Epitopes / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D005798:Genes, Bacterial; D016680:Genome, Bacterial; D023281:Genomics / Q000379:methods; D006801:Humans; D008826:Microbial Sensitivity Tests
chemical_list: D000900:Anti-Bacterial Agents; D001428:Bacterial Vaccines; D000939:Epitopes
keywords: Acinetobacter baumannii; Vaxign; antibiotic resistance; bioinformatics; reverse vaccinology; vaccine candidate