title: Structure-based design of a B cell antigen from B. pseudomallei.
abstract: Burkholderia pseudomallei is the etiological agent of melioidosis, a severe endemic disease in South-East Asia, causing septicemia and organ failure with high mortality rates. Current treatments and diagnostic approaches are largely ineffective. The development of new diagnostic tools and vaccines toward effective therapeutic opportunities against B. pseudomallei is therefore an urgent priority. In the framework of a multidisciplinary project tackling melioidosis through reverse and structural vaccinology, BPSL1050 was identified as a candidate for immunodiagnostic and vaccine development based on its reactivity against the sera of melioidosis patients. We determined its NMR solution structure and dynamics, and by novel computational methods we predicted immunogenic epitopes that once synthesized were able to elicit the production of antibodies inducing the agglutination of the bacterium and recognizing both BPSL1050 and B. pseudomallei crude extracts. Overall, these results hold promise for novel chemical biology approaches in the discovery of new diagnostic and prophylactic tools against melioidosis.
authors.affiliation: †Biomolecular NMR Laboratory, Division of Genetics and Cell Biology, S. Raffaele Scientific Institute, Milan, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Gaudesi
authors.affiliation: ‡Department of Computational Biology, Institute for Molecular Recognition Chemistry, Italian National Research Council, Milan, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Peri
authors.affiliation: †Biomolecular NMR Laboratory, Division of Genetics and Cell Biology, S. Raffaele Scientific Institute, Milan, Italy.
authors.forename: Giacomo
authors.initials: G
authors.lastname: Quilici
authors.affiliation: ‡Department of Computational Biology, Institute for Molecular Recognition Chemistry, Italian National Research Council, Milan, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Gori
authors.affiliation: §Institute of Biotechnology and Biomedicine, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Mario
authors.initials: M
authors.lastname: Ferrer-Navarro
authors.affiliation: §Institute of Biotechnology and Biomedicine, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Oscar
authors.initials: O
authors.lastname: Conchillo-Solé
authors.affiliation: ∥College of Life and Environmental Sciences, University of Exeter, Exeter, United Kingdom.
authors.forename: Rachael
authors.initials: R
authors.lastname: Thomas
authors.affiliation: ⊥Center for Research and Development of Medical Diagnostic Laboratories (CMDL), Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Arnone
authors.initials: A
authors.lastname: Nithichanon
authors.affiliation: ⊥Center for Research and Development of Medical Diagnostic Laboratories (CMDL), Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Ganjana
authors.initials: G
authors.lastname: Lertmemongkolchai
authors.affiliation: ∥College of Life and Environmental Sciences, University of Exeter, Exeter, United Kingdom.
authors.forename: Richard
authors.initials: R
authors.lastname: Titball
authors.affiliation: §Institute of Biotechnology and Biomedicine, Universitat Autònoma de Barcelona, Barcelona, Spain.|#Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Daura
authors.affiliation: ‡Department of Computational Biology, Institute for Molecular Recognition Chemistry, Italian National Research Council, Milan, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Colombo
authors.affiliation: †Biomolecular NMR Laboratory, Division of Genetics and Cell Biology, S. Raffaele Scientific Institute, Milan, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Musco
mesh_terms: D000372:Agglutination Tests; D000595:Amino Acid Sequence; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis / Q000737:chemistry* / Q000494:pharmacology; D000942:Antigens, Bacterial / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D016957:Burkholderia pseudomallei / Q000737:chemistry / Q000187:drug effects* / Q000276:immunology; D018604:Epitope Mapping; D000939:Epitopes / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D006801:Humans; D007106:Immune Sera / Q000737:chemistry / Q000276:immunology; D008554:Melioidosis / Q000097:blood / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D015202:Protein Engineering; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011817:Rabbits; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D013329:Structure-Activity Relationship
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D000939:Epitopes; D007106:Immune Sera; D011994:Recombinant Proteins