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Bayliss, Marc, Donaldson, Matthew I., Nepogodiev, Sergey A., Pergolizzi, Giulia, Scott, Andrew E., Harmer, Nicholas J., Field, Robert A. 
ORCID: https://orcid.org/0000-0001-8574-0275 and Prior, Joann L.
(2017)
Structural characterisation of the capsular polysaccharide expressed by Burkholderia thailandensis strain E555:: wbiI (pKnock-KmR) and assessment of the significance of the 2-O-acetyl group in immune protection.
Carbohydrate Research, 452.
pp. 17-24.
ISSN 0008-6215
Abstract
Burkholderia pseudomallei and its close relative B. mallei are human pathogens that are classified as Tier 1 bio-threat agents. Both organisms have previously been shown to constitutively produce a capsular polysaccharide (CPS) that is both a virulence determinant and protective antigen. Extraction and purification of CPS for use as a potential vaccine candidate requires containment level 3 laboratories which is expensive and time-consuming. B. thailandensis strain E555 is closely related to B. pseudomallei and B. mallei, but is non-pathogenic to humans and based on immunological cross-reactivity has previously been shown to express a B. pseudomallei-like CPS. In this study, capsular polysaccharide isolated from an O-antigen deficient strain of B. thailandensis E555 was identified by 1H and 13C NMR spectroscopy as -3-)-2-O-acetyl-6-deoxy-β-D-manno-heptopyranose-(-1, and identical to that produced by B. pseudomallei. This was further substantiated by anti-CPS monoclonal antibody binding. In connection with the production of CPS fragments for use in glycoconjugate vaccines, we set out to assess the importance or otherwise of the CPS 2-OAc groups in immune protection. To this end conjugates of the native and de-O-acetylated CPS with the Hc fragment of tetanus toxin (TetHc) were used as vaccines in a mouse model of melioidosis. The level of protection provided by deacetylated CPS was significantly lower than that from native, acetylated CPS. In addition, sera from mice vaccinated with the deacetylated CPS conjugate did not recognise native CPS. This suggests that CPS extracted from B. thailandensis can be used as antigen and that the acetyl group is essential for protection.
| Item Type: | Article |
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| Additional Information: | Funding Information: This research was funded by the US Defence Threat Reduction Agency (DTRA) , grant CBBAA12-VAXBT2-1-0032 and the United Kingdom Ministry of Defence . Studies at the JIC were supported by the UK BBSRC Institute Strategic Programme on Understanding and Exploiting Metabolism (MET) [ BB/J004561/1 ] and the John Innes Foundation . MID was supported by a BBSRC Industrial CASE award with Mologic Ltd . We would like to thank Associate Professor Paul Brett at the University of Nevada, Reno School of Medicine for providing purified CPS extracted from B. pseudomallei 1026b for use as a reference in NMR and for providing the method for CPS extraction. Appendix A Publisher Copyright: © 2017 |
| Uncontrolled Keywords: | burkholderia pseudomallei,burkholderia thailandensis,capsular polysaccharide,glycoconjugate vaccine,melioidosis,analytical chemistry,biochemistry,organic chemistry,sdg 3 - good health and well-being ,/dk/atira/pure/subjectarea/asjc/1600/1602 |
| Faculty \ School: | Faculty of Science > School of Chemistry, Pharmacy and Pharmacology |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 04 Sep 2024 09:35 |
| Last Modified: | 25 Sep 2024 18:06 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/96511 |
| DOI: | 10.1016/j.carres.2017.09.011 |
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