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dc.contributor.authorWikraiphat, Chanthiwa
dc.contributor.authorSaiprom, Natnaree
dc.contributor.authorTandhavanant, Sarunporn
dc.contributor.authorHeiss, Christian
dc.contributor.authorAzadi, Parastoo
dc.contributor.authorWongsuvan, Gumphol
dc.contributor.authorTuanyok, Apichai
dc.contributor.authorHolden, Matthew
dc.contributor.authorBurtnick, Mary N
dc.contributor.authorBrett, Paul J
dc.contributor.authorPeacock, Sharon J
dc.contributor.authorChantratita, Narisara
dc.date.accessioned2015-05-13T11:31:05Z
dc.date.available2015-05-13T11:31:05Z
dc.date.issued2015-05
dc.identifier.citationWikraiphat , C , Saiprom , N , Tandhavanant , S , Heiss , C , Azadi , P , Wongsuvan , G , Tuanyok , A , Holden , M , Burtnick , M N , Brett , P J , Peacock , S J & Chantratita , N 2015 , ' Colony morphology variation of Burkholderia pseudomallei is associated with antigenic variation and O-polysaccharide modifications ' , Infection and Immunity , vol. 83 , no. 5 , pp. 2127-2138 . https://doi.org/10.1128/IAI.02785-14en
dc.identifier.issn0019-9567
dc.identifier.otherPURE: 178073721
dc.identifier.otherPURE UUID: 42aa20db-b830-428c-a09f-fedd4f747655
dc.identifier.otherPubMed: 25776750
dc.identifier.otherScopus: 84928199677
dc.identifier.otherORCID: /0000-0002-4958-2166/work/60196503
dc.identifier.urihttp://hdl.handle.net/10023/6641
dc.descriptionThis work was supported by the Thailand Research Fund (grantTRG5580004), the Wellcome Trust, United Kingdom, and the Department of Energy-funded Center for Plant and Microbial Complex Carbohydrates (grant DE-FG09-93ER-20097). N.C. was supported by the Wellcome Trust (grant 087769/Z/08/Z).en
dc.description.abstractBurkholderia pseudomallei is a CDC Tier 1 select agent that causes melioidosis, a severe disease in humans and animals. Persistent infections are common and there is currently no vaccine available. Lipopolysaccharide (LPS) is a potential vaccine candidate. B. pseudomallei expresses three serologically distinct LPS types. The predominant O-polysaccharide (OPS) is an unbranched heteropolymer with repeating d-glucose and 6-deoxy-l-talose residues in which the 6-deoxy-l-talose residues are variably substituted with O-acetyl and O-methyl modifications. We observed that primary clinical B. pseudomallei isolates with mucoid and non-mucoid colony morphologies from the same sample expressed different antigenic types distinguishable using a LPS-specific monoclonal antibody (Mab). Mab reactive (non-mucoid) and non-reactive (mucoid) strains from the same patient exhibited identical LPS banding patterns by silver staining and indistinguishable genotypes. We hypothesized that LPS antigenic variation reflected modification of the OPS moieties. Mutagenesis of three genes involved in LPS synthesis was performed in B. pseudomallei K96243. Loss of Mab reactivity was observed in both wbiA (encoding a 2-O-acetyltransferase) and wbiD (putative methyl transferase) mutants. The structural characteristics of the OPS moieties from isogenic non-mucoid strain 4095a and mucoid strain 4095c were further investigated. Utilizing NMR spectroscopy, we found that B. pseudomallei 4095a and 4095c OPS antigens exhibited substitution patterns that differed from the prototypic OPS structure. Specifically, 4095a lacked 4-O-acetylation while 4095c lacked both 4-O-acetylation and 2-O-methylation. Our studies indicate that B. pseudomallei OPS undergoes antigenic variation and suggest that the 9D5 Mab recognizes a conformational epitope that is influenced by both O-acetyl and O-methyl substitution patterns.
dc.language.isoeng
dc.relation.ispartofInfection and Immunityen
dc.rightsCopyright © 2015, American Society for Microbiology. All Rights Reserved. This is an Accepted Manuscript of an article published in Infection and Immunity on 16 March 2015, available online: http://iai.asm.org/content/83/5/2127en
dc.subjectMelioidosisen
dc.subjectBurkholderia pseudomalleien
dc.subjectLipopolysaccharideen
dc.subjectO-polysaccharideen
dc.subjectR Medicineen
dc.subjectQR Microbiologyen
dc.subjectNDASen
dc.subject.lccRen
dc.subject.lccQRen
dc.titleColony morphology variation of Burkholderia pseudomallei is associated with antigenic variation and O-polysaccharide modificationsen
dc.typeJournal articleen
dc.description.versionPostprinten
dc.contributor.institutionUniversity of St Andrews.School of Medicineen
dc.contributor.institutionUniversity of St Andrews.Infection Groupen
dc.contributor.institutionUniversity of St Andrews.Biomedical Sciences Research Complexen
dc.identifier.doihttps://doi.org/10.1128/IAI.02785-14
dc.description.statusPeer revieweden


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