Burkholderia pseudomallei (Bp) and Burkholderia mallei (Bm), the etiologic agents of melioidosis and glanders, respectively, cause severe disease in both humans and animals. Studies have highlighted the importance of Bp and Bm lipopolysaccharides (LPS) as vaccine candidates. Here we describe the synthesis of seven oligosaccharides as the minimal structures featuring all of the reported acetylation/methylation patterns associated with Bp and Bm LPS O-antigens (OAgs). Our approach is based on the conversion of an L-rhamnose into a 6-deoxy-L-talose residue at a late stage of the synthetic sequence. Using biochemical and biophysical methods, we demonstrate the binding of several Bp and Bm LPS-specific monoclonal antibodies with terminal OAg residues. Mice immunized with terminal disaccharide-CRM197 constructs produced high-titer antibody responses that crossreacted with Bm-like OAgs. Collectively, these studies serve as foundation for the development of novel therapeutics, diagnostics, and vaccine candidates to combat diseases caused by Bp and Bm.Melioidosis and glanders are multifaceted infections caused by gram-negative bacteria. Here, the authors synthesize a series of oligosaccharides that mimic the lipopolysaccharides present on the pathogens' surface and use them to develop novel glycoconjugates for vaccine development.
synthesis, lipopolysaccharides, O-antigen, monoclonal antibodies, glycoconjugates, Burkholderia pseudomallei, melioidosis, Burkholderia mallei
NCBI PubMed ID: 28740137Publication DOI: 10.1038/s41467-017-00173-8Journal NLM ID: 101528555Publisher: London: Nature Publishing Group
Correspondence: charles.gauthier@iaf.inrs.ca; pbrett@southalabama.edu; charles.gauthier@iaf.inrs.ca
Institutions: Department of Chemistry, Wroclaw University of Environmental and Life Sciences, C. K. Norwida 25, Wroclaw, 50-375, Poland, Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Prince of Songkla University, 15, Kanjanavanit Road, 90112, Songkhla, Thailand, Institut Lavoisier de Versailles, CNRS-UMR 8180, Universite de Versailles Saint-Quentin-en-Yvelines, Universite Paris-Saclay, 45, Avenue des Etats-Unis, Versailles, 78035, France, Department of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University, 420/6 Rajvithi Road, Bangkok, 10400, Thailand, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, 420/6 Rajvithi Road, Bangkok, 10400, Thailand, Department of Chemical Sciences, Universita di Napoli Federico II, Complesso Universitario Monte S. Angelo, Via Cintia 4, Naples, I-80126, Italy, Department of Microbiology and Immunology, University of Nevada School of Medicine, 1664, N. Virginia Street, Reno, Nevada, 89557, USA, Department of Microbiology and Immunology, University of South Alabama, 610, Clinic Drive, Mobile, Alabama, 36688, USA, Institut de Chimie IC2MP, CNRS-UMR 7285, Equipe Synthese Organique, Groupe Glycochimie, Universite de Poitiers, 4, rue Michel Brunet, Poitiers, 86073, France, INRS-Institut Armand-Frappier, Universite du Quebec, 531, Boulevard des Prairies, Laval (Quebec), Canada, H7V 1B7
Methods: 13C NMR, 1H NMR, X-ray, SDS-PAGE, TLC, ELISA, Western blotting, chemical synthesis, MALDI-TOF MS, STD NMR, UV, glycosylation, immunofluorescence microscopy, SPR, immunization, HR-ESI-MS, biotinylation, immunogenicity evaluation
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