Melioidosis and glanders, respectively caused by the Gram-negative bacteria Burkholderia pseudomallei (Bp) and Burkholderia mallei (Bm), are considered as urgent public health issues in developing countries and potential bioterrorism agents. Bp and Bm lipopolysaccharides (LPS) have been identified as attractive vaccine candidates for the development of prophylactic measures against melioidosis and glanders. Bp and Bm express structurally similar LPSs wherein the O-antigen (OAg) portion consists of a heteropolymer whose repeating unit is a disaccharide composed of d-glucose and 6-deoxy-l-talose residues, the latter being diversely acetylated and methylated. Herein we report the synthesis of two tetrasaccharides mimicking the main substitution epitopes of Bp and Bm LPS OAgs. The assembly of the tetrasaccharides was achieved using a sequential glycosylation strategy while relying on the late-stage epimerization of the inner rhamnose into a 6-deoxy-l-talose residue. We show that these synthetic compounds strongly react with culture-confirmed Thai melioidosis patient serum and closely mimic the antigenicity of native Bp OAg. Our results suggest that these tetrasaccharides could be suitable candidates for the development of vaccines and/or diagnostic tools against melioidosis and glanders.
synthesis, Burkholderia, epitopes, Burkholderia pseudomallei, 6-deoxy-L-talose, Synthetic, melioidosis, Burkholderia mallei
NCBI PubMed ID: 31513223Publication DOI: 10.1039/c9ob01711aJournal NLM ID: 101154995Publisher: The Royal Society of Chemistry
Correspondence: charles.gauthier@iaf.inrs.ca
Institutions: Centre Armand-Frappier Santé Biotechnologie, Institut national de la recherche scientifique (INRS), 531, boul. des Prairies, Laval (Québec), Canada H7V 1B7, 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 Microbiology and Immunology, University of Nevada, Reno School of Medicine, 1664, N. Virginia Street, Reno, Nevada 89557, USA
Methods: 13C NMR, 1H NMR, TLC, ELISA, chemical synthesis, UV, optical rotation measurement, ESI-QTOF-MS, flash chromatography
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