Evidence for a New Type of Outer Membrane Lipid in Oral Spirochete Treponema denticola

Schultz, Christian; Wolf, Violetta; Lange, R; Mertens, Erich; Wecke, Jörg; Naumann, Dieter; Zähringer, Ulrich

doi:10.1074/jbc.273.25.15661

Cited by 77 publications

(92 citation statements)

References 40 publications

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“…On the other hand, the cell membrane components isolated displayed LTA-like elements such as sugar, high phosphate, and alanine similar to that previously identified in Treponema denticola (68). This similarity was further supported by isolation and analysis of the dephosphorylated glycosyl part of the repeating units, which exhibited a low number of large repeats composing 20 -30 sugars in T. maltophilum and a high number of small repeats containing ϳ5 sugars in T. brennaborense.…”

Section: Involvement Of Tlr-4 In Raw2647 Cell Stimulation By Treponesupporting

confidence: 54%

Toll-like Receptor-2 Mediates Treponema Glycolipid and Lipoteichoic Acid-induced NF-κB Translocation

Opitz

Schröder

Spreitzer

et al. 2001

Journal of Biological Chemistry

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207

141

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Recently Toll-like receptors (TLRs) have been found to be involved in cellular activation by microbial products, including lipopolysaccharide, lipoproteins, and peptidoglycan. Although for these ligands the specific transmembrane signal transducers TLR-4, TLR-2, or TLR-2 and -6 have now been identified, the molecular basis of recognition of lipoteichoic acids (LTAs) and related glycolipids has not been completely understood. In order to determine the role of TLRs in immune cell activation by these stimuli, experiments involving TLR-2-negative cell lines, TLR-expression plasmids, macrophages from TLR-4-deficient C3H/HeJ-mice, and inhibitory TLR-4/MD-2 antibodies were performed. Glycolipids from Treponema maltophilum and Treponema brennaborense, as well as highly purified LTAs from Staphylococcus aureus and Bacillus subtilis exhibited TLR-2 dependence in nuclear factor B activation and cytokine induction; however, T. brennaborense additionally appeared to signal via TLR-4. Fractionation of the T. brennaborense glycolipids by hydrophobic interaction chromatography and subsequent cell stimulation experiments revealed two peaks of activity, one exhibiting TLR-2-, and a second TLR-4-dependence. Furthermore, we show involvement of the signaling molecules MyD88 and NIK in cell stimulation by LTAs and glycolipids by dominant negative overexpression experiments. In summary, the results presented here indicate that TLR-2 is the main receptor for Treponema glycolipid and LTA-mediated inflammatory response.

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Section: Involvement Of Tlr-4 In Raw2647 Cell Stimulation By Treponesupporting

confidence: 54%

Toll-like Receptor-2 Mediates Treponema Glycolipid and Lipoteichoic Acid-induced NF-κB Translocation

Opitz

Schröder

Spreitzer

et al. 2001

Journal of Biological Chemistry

Self Cite

207

141

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“…1 most likely encodes the GT needed for this synthesis. In an analogous manner to S. pneumoniae, this lipid may also be the anchor to the complex outer membrane sheath lipid OML521 in T. denticola (38). Additional homologs from other pathogens, not shown here, were also found in, for example, Streptococcus mutans, Clostridium acetobutylicum, and Streptococcus equi.…”

Section: Discussionmentioning

confidence: 81%

Sequence Properties of the 1,2-Diacylglycerol 3-Glucosyltransferase from Acholeplasma laidlawiiMembranes

Berg

Edman

et al. 2001

Journal of Biological Chemistry

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Synthesis of the nonbilayer-prone ␣-monoglucosyldiacylglycerol (MGlcDAG) is crucial for bilayer packing properties and the lipid surface charge density in the membrane of Acholeplasma laidlawii. The gene for the responsible, membrane-bound glucosyltransferase (alMGS) (EC 2.4.1.157) was sequenced and functionally cloned in Escherichia coli, yielding MGlcDAG in the recombinants. Similar amino acid sequences were encoded in the genomes of several Gram-positive bacteria (especially pathogens), thermophiles, archaea, and a few eukaryotes. All of these contained the typical EX 7 E catalytic motif of the CAZy family 4 of ␣-glycosyltransferases. The synthesis of MGlcDAG by a close sequence analog from Streptococcus pneumoniae (spMGS) was verified by polymerase chain reaction cloning, corroborating a connection between sequence and functional similarity for these proteins. However, alMGS and spMGS varied in dependence on anionic phospholipid activators phosphatidylglycerol and cardiolipin, suggesting certain regulatory differences. Fold predictions strongly indicated a similarity for alMGS (and spMGS) with the two-domain structure of the E. coli MurG cell envelope glycosyltransferase and several amphipathic membrane-binding segments in various proteins. On the basis of this structure, the alMGS sequence charge distribution, and anionic phospholipid dependence, a model for the bilayer surface binding and activity is proposed for this regulatory enzyme.Lipids are the local environment for most integral and peripheral membrane proteins, which often depend on the lipids for optimal function. The large diversity of lipids and the differences in composition and properties between membranes have made it difficult to find out common features of bilayer organization and how lipids and proteins are cooperating in local processes. Lipid-synthesizing pathways have been mapped for the most common types of lipids, and several of the corresponding enzymes catalyzing these reactions have been characterized. However, when it comes to the connection between regulation of bilayer properties and enzyme structure, very little is known (1). So far, only a few lipid-synthesizing enzymes have been crystallized. Which structural properties are involved in the catalytic mechanism of these lipid enzymes, and how are the membrane properties sensed (1)?In the well characterized plasma membrane of Acholeplasma laidlawii, the lipid composition is regulated in a manner to maintain (i) lipid phase equilibria, close to a potential bilayer to nonbilayer transition, (ii) a nearly constant radius of spontaneous curvature, and (iii) a certain anionic surface charge density of the lipid bilayer. The synthesis of the major nonbilayer-prone lipid in this membrane, monoglucosyldiacylglycerol (MGlcDAG) 1 (Scheme 1, step I), plays an important role to fulfill the two first points above but also the third, since it is strongly regulated by negatively charged lipids (e.g. the major in vivo lipid phosphatidylglycerol (PG)) (2). MGlcDAG is consecutively processed into...

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“…The outer sheath of spirochetes is reported to be unusual in its composition and properties compared to the outer membrane of typical Gramnegative bacteria. Previous studies with T. denticola lipopolysaccharide (LPS) are contradictory, ranging from the detection of LPS-like material (30) to the absence of any LPS structural components (31). TDE1419-TDE1441 encode various glycosyl hydrolases and RfbAB that may be involved in synthesis of surface polysaccharides; however, other enzymes for synthesis of Lipid A, KDO, or other LPS components are absent.…”

Section: Resultsmentioning

confidence: 99%

Comparison of the genome of the oral pathogen Treponema denticola with other spirochete genomes

Seshadri

Myers

Tettelin

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

251

314

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We present the complete 2,843,201-bp genome sequence of Treponema denticola (ATCC 35405) an oral spirochete associated with periodontal disease. Analysis of the T. denticola genome reveals factors mediating coaggregation, cell signaling, stress protection, and other competitive and cooperative measures, consistent with its pathogenic nature and lifestyle within the mixed-species environment of subgingival dental plaque. Comparisons with previously sequenced spirochete genomes revealed specific factors contributing to differences and similarities in spirochete physiology as well as pathogenic potential. The T. denticola genome is considerably larger in size than the genome of the related syphiliscausing spirochete Treponema pallidum. The differences in gene content appear to be attributable to a combination of three phenomena: genome reduction, lineage-specific expansions, and horizontal gene transfer. Genes lost due to reductive evolution appear to be largely involved in metabolism and transport, whereas some of the genes that have arisen due to lineage-specific expansions are implicated in various pathogenic interactions, and genes acquired via horizontal gene transfer are largely phagerelated or of unknown function.

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Evidence for a New Type of Outer Membrane Lipid in Oral Spirochete Treponema denticola

Cited by 77 publications

References 40 publications

Toll-like Receptor-2 Mediates Treponema Glycolipid and Lipoteichoic Acid-induced NF-κB Translocation

Toll-like Receptor-2 Mediates Treponema Glycolipid and Lipoteichoic Acid-induced NF-κB Translocation

Sequence Properties of the 1,2-Diacylglycerol 3-Glucosyltransferase from Acholeplasma laidlawiiMembranes

Comparison of the genome of the oral pathogen Treponema denticola with other spirochete genomes

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