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dc.contributor.authorTomek, Markus B
dc.contributor.authorMaresch, Daniel
dc.contributor.authorWindwarder, Markus
dc.contributor.authorFriedrich, Valentin
dc.contributor.authorJanesch, Bettina
dc.contributor.authorFuchs, Kristina
dc.contributor.authorNeumann, Laura
dc.contributor.authorNimeth, Irene
dc.contributor.authorZwickl, Nikolaus F
dc.contributor.authorDohm, Juliane C
dc.contributor.authorEverest-Dass, Arun
dc.contributor.authorKolarich, Daniel
dc.contributor.authorHimmelbauer, Heinz
dc.contributor.authorAltmann, Friedrich
dc.contributor.authorSchaeffer, Christina
dc.date.accessioned2019-09-09T00:18:02Z
dc.date.available2019-09-09T00:18:02Z
dc.date.issued2018
dc.identifier.issn1664-302X
dc.identifier.doi10.3389/fmicb.2018.02008
dc.identifier.urihttp://hdl.handle.net/10072/387029
dc.description.abstractThe cell surface of the oral pathogen Tannerella forsythia is heavily glycosylated with a unique, complex decasaccharide that is O-glycosidically linked to the bacterium's abundant surface (S-) layer, as well as other proteins. The S-layer glycoproteins are virulence factors of T. forsythia and there is evidence that protein O-glycosylation underpins the bacterium's pathogenicity. To elucidate the protein O-glycosylation pathway, genes suspected of encoding pathway components were first identified in the genome sequence of the ATCC 43037 type strain, revealing a 27-kb gene cluster that was shown to be polycistronic. Using a gene deletion approach targeted at predicted glycosyltransferases (Gtfs) and methyltransferases encoded in this gene cluster, in combination with mass spectrometry of the protein-released O-glycans, we show that the gene cluster encodes the species-specific part of the T. forsythia ATCC 43037 decasaccharide and that this is assembled step-wise on a pentasaccharide core. The core was previously proposed to be conserved within the Bacteroidetes phylum, to which T. forsythia is affiliated, and its biosynthesis is encoded elsewhere on the bacterial genome. Next, to assess the prevalence of protein O-glycosylation among Tannerella sp., the publicly available genome sequences of six T. forsythia strains were compared, revealing gene clusters of similar size and organization as found in the ATCC 43037 type strain. The corresponding region in the genome of a periodontal health-associated Tannerella isolate showed a different gene composition lacking most of the genes commonly found in the pathogenic strains. Finally, we investigated whether differential cell surface glycosylation impacts T. forsythia's overall immunogenicity. Release of proinflammatory cytokines by dendritic cells (DCs) upon stimulation with defined Gtf-deficient mutants of the type strain was measured and their T cell-priming potential post-stimulation was explored. This revealed that the O-glycan is pivotal to modulating DC effector functions, with the T. forsythia-specific glycan portion suppressing and the pentasaccharide core activating a Th17 response. We conclude that complex protein O-glycosylation is a hallmark of pathogenic T. forsythia strains and propose it as a valuable target for the design of novel antimicrobials against periodontitis.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherFrontiers Media
dc.relation.ispartofpagefrom2008-1
dc.relation.ispartofpageto2008-18
dc.relation.ispartofjournalFrontiers in Microbiology
dc.relation.ispartofvolume9
dc.subject.fieldofresearchSoil sciences
dc.subject.fieldofresearchMicrobiology
dc.subject.fieldofresearchMedical microbiology
dc.subject.fieldofresearchcode4106
dc.subject.fieldofresearchcode3107
dc.subject.fieldofresearchcode3207
dc.subject.keywordsScience & Technology
dc.subject.keywordsLife Sciences & Biomedicine
dc.subject.keywordscarbohydrate-active enzymes
dc.subject.keywordsglycosyltransferase
dc.titleA General Protein O-Glycosylation Gene Cluster Encodes the Species-Specific Glycan of the Oral Pathogen Tannerella forsythia: O-Glycan Biosynthesis and Immunological Implications
dc.typeJournal article
dc.type.descriptionC1 - Articles
dcterms.bibliographicCitationTomek, MB; Maresch, D; Windwarder, M; Friedrich, V; Janesch, B; Fuchs, K; Neumann, L; Nimeth, I; Zwickl, NF; Dohm, JC; Everest-Dass, A; Kolarich, D; Himmelbauer, H; Altmann, F; Schaeffer, C, A General Protein O-Glycosylation Gene Cluster Encodes the Species-Specific Glycan of the Oral Pathogen Tannerella forsythia: O-Glycan Biosynthesis and Immunological Implications, Frontiers in Microbiology, 2018, 9, pp. 2008-1 - 2008-18
dcterms.dateAccepted2018-08-09
dcterms.licensehttps://creativecommons.org/licenses/by/4.0/
dc.date.updated2019-09-09T00:11:50Z
dc.description.versionVersion of Record (VoR)
gro.rights.copyright© 2019 Søndberg, Sinha, Gerdes and Semsey. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
gro.hasfulltextFull Text
gro.griffith.authorKolarich, Daniel
gro.griffith.authorEverest-Dass, Arun


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