O Lüderitz

Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Baden-Württemberg, Germany

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Publications (153)441.75 Total impact

  • Chris GALANOS, Otto LÜDERITZ
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    ABSTRACT: Lipopolysaccharides interact with complement only when they are present in a state of high aggregation with a high apparent molecular weight. Lipopolysaccharides in uniform salt forms prepared by electrodialysis and neutralization with different bases exhibited distinct differences in their anticomplementary activity which correlated with differences in their sedimentation coefficients.Conversion of smooth (S) form lipopolysaccharides into the low-molecular-weight triethylamine form completely abolished their anti-complementary activity while conversion into the highmolecular-weight sodium form increased their activity. In contrast, a similar treatment of highly defective Re and Rd rough (R) form lipopolysaccharides had no effect on their ability to interact with complement. Both the triethylamine and sodium forms were strongly anti-complementary despite large differences in their molecular weight. This was found to be due to the property of R lipopolysaccharides to reaggregate into a large-molecular-weight form through absorption of Mg2+ and Ca2+ present in the guinea pig serum used as complement source. Defective lipopolysaccharides derived from the Ra and Rb classes showed only negligible anti-complementary activity which did not increase by conversion into salt forms with high molecular weight.
    European Journal of Biochemistry. 06/2008; 65(2):403 - 408.
  • 05/2008: pages 187 - 199; , ISBN: 9780470719060
  • Annals of the New York Academy of Sciences 12/2006; 133(2):349 - 374. · 4.38 Impact Factor
  • O. Westphal, O. Lüderitz
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    ABSTRACT: Lipopolysaccharide gramnegativer Bakterien sind Träger verschiedener charakteristischer biologischer Wirkungen. Ihre chemische Erforschung ist daher von erheblichem, u. a. auch praktisch-klinischem Interesse. Es wird über Verfahren zur Isolierung und Reindarstellung der Lipopolysaccharide sowie Methoden zu ihrer Spaltung in einzelne Komponenten berichtet. Ergebnisse der qualitativen und quantitativen Bausteinanalyse der Polysaccharid- und Lipoid-Komponenten und Untersuchungen über den Zusammenhang zwischen dem chemischen Bau und der biologischen Funktion einzelner Komponenten werden diskutiert.
    Angewandte Chemie 01/2006; 66(13‐14):407 - 417.
  • O. Westphal, O. Lüderitz
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    ABSTRACT: In den letzten Jahren wurde, hauptschlich bei Bakterien, eine neue Klasse von Desoxyzuckern aufgefunden und — gemeinsam mit den Arbeitskreisen von A. M. Staub und E. Lederer — als 3.6-Didesoxyhexosen aufgeklrt. Von den theoretisch möglichen acht Stereoisomeren sind bislang wenigstens fünf natürliche Vertreter, darunter zwei Paare von optischen Antipoden, bekannt. Ihre Isolierung, Strukturaufklrung und Synthese sowie Nachweisverfahren werden beschrieben. In Zusammenarbeit mit F. Kauffmann wurden umfangreiche Zuckerbaustein-Analysen von Polysacchariden (O-Antigenen) bei Salmonellen u. a. durchgeführt; 3.6-Didesoxy-hexosen treten hufig auf und sind charakteristisch für bestimmte Serogruppen. Als Bausteine spezifischer Polysaccharide in der bakteriellen Zellwand besitzen die jeweils terminal gebundenen 3.6-Didesoxy-hexosen vielfach immunologische Funktion als determinante (spezifitts-bestimmende) Endgruppen (mit A. M. Staub und R. Tinelli). Dies wurde u. a. durch Darstellung eines künstlichen Antigens mit Colitose (3-Desoxy-L-fucose) als determinanter Gruppe demonstriert. Die Immunisierung geeigneter Tiere führte nicht nur zu Antikörpern gegen Colitose, sondern auch gegen einige pathogene Bakterien, welche colitose-haltige Zellwand-Polysaccharide bilden (E. coli O 111 u. a.). Einige biochemische und genetische Aspekte im Zusammenhang mit 3.6-didesoxyhexose-haltigen bakteriellen Zellwand-Polysacchariden werden erörtert und diskutiert.
    Angewandte Chemie 01/2006; 72(23):881 - 891.
  • O. Lüderitz, O. Westphal
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    ABSTRACT: Enterobacteriaceen bilden als äußere Zelloberfläche eine Zellwand, die aus einer rigiden Struktur (Murein) besteht, auf welche Protein, Lipoid und Polysaccharid aufgelagert sind. Bei den bakteriellen Wildformen (S-Formen) ist das Polysaccharid species-spezifisch und Träger der serologisch determinanten Gruppen des jeweiligen O-Antigens. Es handelt sich um Heteropolysaccharide, an deren Aufbau bis zu acht verschiedene Monosaccharide beteiligt sein können. Gebunden an Lipoid A, stellen die Lipopolysaccharide der Zellwände die Endotoxine dieser Bakterien dar. – In den letzten Jahren ist die Struktur der enterobakteriellen Zellwand-Polysaccharide durch chemische, immunchemische, biochemische und genetische Untersuchungen besonders bei Salmonellen weitgehend aufgeklärt worden. Sie sind aus zwei Anteilen aufgebaut: einem allen Species gemeinsamen Kern- oder Basal-Polysaccharid, an welches (bei den S-Formen) längere species-spezifische Seitenketten gebunden sind, die aus sich wiederholenden Oligosaccharid-Einheiten bestehen. – Durch spontane S → R-Mutation entstehen R-Formen, welche sich als Verlust-Mutanten der Wildformen in Bezug auf die Biosynthese des kompletten Zellwand-Polysaccharids erwiesen haben. Gegenüber der Vielfalt an serologischen Spezifitäten der S-Formen findet man bei R-Formen nur einige wenige Serotypen (RI, RII u. a.) Die R-Polysaccharide entsprechen Zwischenstufen in der Biosynthese des Polysaccharids der Wildform, und die S → R-Mutation führt jeweils zum Verlust (oder zur Blockierung) eines am Aufbau des S-Polysaccharids beteiligten Enzyms (Transferase, Synthetase). Neuerdings konnten viele bisher unbekannte Verlust-Mutanten isoliert und analysiert werden, wodurch zahlreiche biosynthetische Zwischenstufen des Zellwand-Polysaccharids, z.B. von Salmonella minnesota, der direkten Analyse zugänglich wurden. – Nach diesen Untersuchungen bestehen die Zellwand-Polysaccharide der Salmonellen aus einer Polyheptosephosphat-Grundkette, welche über Ketodesoxyoctonsäure (KDO) an Lipoid A gebunden ist. An die Grundkette sind Pentasaccharid-Einheiten von gebunden (RII-Struktur). Alle übrigen R-Formen sind strukturell Verlust-Mutanten von RII. In den kompletten Polysacchariden der Salmonella-S-Formen sind an das terminale N-Acetylglucosamin der RII-Struktur die sich wiederholenden Oligosaccharid-Einheiten der spezifischen Seitenketten gebunden.
    Angewandte Chemie 01/2006; 78(3):172 - 185.
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    ABSTRACT: A pentaacyl precursor of lipid A biosynthesis, termed precursor Ib, and a structural isomer have been chemically synthesized. These compounds were, in comparison to synthetic Escherichia-coli type lipid A or lipopolysaccharide, analyzed for their activity in typical endotoxin test systems. It was found that both precursor Ib and the isomer exhibited similar or only slightly lower pyrogenic, lethal and Shwartzman-phenomenon-inducing activity than lipid A. All preparations were comparable in their B-lymphocyte mitogenicity, macrophage-activating capacity and immunoreactivity towards lipid A antisera. The proton nuclear magnetic resonance spectra of the 1-dephospho derivative of synthetic and bacterial precursor Ib were indistinguishable proving that the previously proposed structure for precursor Ib is correct.
    European Journal of Biochemistry. 03/2005; 169(1):27 - 31.
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    ABSTRACT: From the wild types (S forms) of Salmonella minnesota and Salmonella ruiru R mutants (R forms) were isolated which produce hexose-less cell wall lipopolysaccharides of chemotype Rd. These lipopolysaccharides are composed of lipid A (glucosamine, long-chain fatty acids, phosphoric acid), 2-keto-3-deoxy-octonate (KDO), and l-glycero-d-manno-heptose (heptose), while those of the parent S forms contain additional galactosamine, glucosamine, galactose and glucose. R mutants with lipopolysaccharides of chemotype Rd could be differentiated into two groups, Rd1 and Rd2.Group Rd1 comprises the S. minnesota mutants mR7 and mRz. Their lipopolysaccharides contain about 14% heptose. Partial hydrolysis of the mR7 lipopolysaccharide resulted in the formation of three main split products: lipid A, mR7A and mR7B. mR7A was identified as free 2-keto-3-deoxy-octonate, while mR7B was composed of heptose and 2-keto-3-deoxy-octonate. Depending on the method applied for the estimation of 2-keto-3-deoxy-octonate, the molar ratio of heptose/2-keto-3-deoxy-octonate was found to be 2:0.3 (on the basis of the thiobarbituric acid reaction) or 2:1 (according to the semicarbazide reaction). When permethylated mR7B was methanolyzed and the products analyzed by gas chromatography, two peaks (7.4 and 15.0 min) were observed. The 7.4 min peak was identical with one of the two peaks (7.4 and 9.6 min) obtained with permethylated authentic d-glycero-l-manno-heptose, the optical antipode of the bacterial heptose. The second peak at 15.0 min, which comprised about the same area as the 7.4 min peak, was derived from a partially methylated heptose. It is concluded that mR7B represents a heptose disaeeharide linked to 2-keto-3-deoxy-octonate and that such units are present in Rd1 lipopolysaccharides as terminal, nonreducing residues of the structure: heptosyl → heptosyl → 2-keto-3-deoxy-octonate–.Group Rd2 comprises the S. minnesota mutants mR3 and mR4 and the S. ruiru mutant rR3. Their lipopolysaccharides contain about 7% neptose. By partial hydrolysis of the mR3 lipopolysaccharide four main split products were obtained: lipid A, mR3A, mR3B and mR3C. Fraction mR3A was identified with free 2-keto-3-deoxy-octonate. mR3B contained heptose, phosphate and ethanolamine in a molar ratio of 1:1:1, and, in addition, 1 mole (by thiobarbituric acid reaction) or 3 moles (by semicarbacide reaction) of 2-keto-3-deoxy-octonate. mR3C contained heptose and 2-keto-3-deoxy-octonate in a ratio of 1:1 (thiobarbituric acid reaction) or 1:2 (semicarbacide reaction), but no phosphate or ethanolamine. mR3B and mR3C were methylated, the products methanolyzed and analyzed by gas chromatography, From both oligosaccharides only one heptose peak (7.4 min) was obtained which was identical with the faster peak observed with mR7B and authentic heptose. It is concluded that in the mR3 lipopolysaccharide, and generally in Rd2 lipopolysaccharides, heptose is exclusively linked as a terminal, non-reducing monosaccharide, presumably to 2-keto-3-deoxy-octonate: heptosyl → 2-keto-3-deoxy-octonate–.The results indicate that Rd2 lipopolysaccharides act as precursors of Rd1 lipopolysaccharides in the biosynthesis of the wild type lipopolysaccharide and that the Rd1 structure (Hep → Hep → KDO –) is formed by transfer of one heptose unit to Rd2 lipopolysaccharides (with terminal Hep-KDO).Biosynthetic studies demonstrated that Rd1 lipopolysaccharides, but not Rd2 lipopolysaccharides, function as acceptor for the enzymatic incorporation of glucose from UDP-glucose. Although the Rd1 mutants, mR7 and mRz, synthesize identical lipopolysaccharides, they are distinct regarding their enzymatic block involving the glucose anabolism. mR7 lacks glucosyl- I-transferase activity, while mRz is defective in the enzyme UDP-glucose-synthetase. - Rd2 mutants, with the incomplete heptosyl-KDO core, are deficient with respect to the transfer of the second heptosyl residue to the first heptose; but they do contain-as expected-glucosyl-I-transferase which catalyzes the incorporation of glucose (glucose I) into the complete heptosyl- heptosyl-KDO core of Rd1 lipopolysaccharides to form the glucosyl-heptosyl-heptosyl-KDO structure of Salmonella Rc lipopolysaccharides.Serologically, heptose proved to be an inhibitor of precipitation in both systems, mR7lanti mR7 (Rd1 system) and mR3/anti mR3 (Rd2 system), which is in agreement with the concept of terminal, non-reducing heptose units occurring in both Rd1 and Rd2 lipopolysaccharides. However, in hemagglutination inhibition tests, the lipopolysaccharides of group Rd2 do not show serological cross-reaction with Rd2 lipopolysaccharides, and vice versa.
    European Journal of Biochemistry. 03/2005; 1(2):216 - 232.
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    ABSTRACT: Fractionation of the O-polysaccharide derived from Salmonella zuerich (1, 9, 27, 46) on a concanavalin A polymer permitted immunological and chemical analysis on the different fractions. The S. zuerich O-poly-saccharide preparation is composed of two distinct populations of molecules: one, ZBI−, devoid of O-antigenic determinant 1, and the other, ZB1+, carrying the determinant 1. This determinant is linked to the presence of d-glUCOSyl residues on the side chain. O-polysaccharide molecules 1−, devoid of d-glucose, are shown to carry simultaneously both determinants 27 and 46. These determinants are not evenly distributed on the molecules. The expression of determinants 46 (-[Tyvl-βMan-, where Tyv = tyvelose) seems to be restricted to a distinct specific configuration, and it is altered by the presence of either determinant 27 (-[Tyv]-αMan-) or determinant 1 (Glc-Gal-) in the close neighbourhood. Molecules 1+ are partially or completely substituted by glucosyl residues and react with anti-I antibodies. They are characterized by the same uneven distribution of determinants 27 and 46 as molecules ZBI−. In conclusion, the O-polysaccharide chains are heterogeneous. They contain simultaneously factors 27, 46, and often also 1.
    European Journal of Biochemistry. 03/2005; 125(2):431 - 436.
  • H. J. Risse, O. Lüderitz, O. Westphal
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    ABSTRACT: About 30 R mutants derived from Salmonella minnesota and Salmonella ruiru and the corresponding wild-type strains were analysed comparatively for the presence of enzymes catalyzing the synthesis of UDP-glucose, UDP-galactose, UDP-N-acetylglucosamine and UDP-N-acetylgalactosamine.In the biosynthesis of the corresponding O antigens these UDP-sugars function as precursors, whose sugar residues are transferred on to the growing polysaccharide by specific transferases. In cell-free extracts of the strains the following enzyme activities were determined: (quantitatively) hexokinase, phosphoglucomutase, UDP-glucose synthetase and UDP-galactose-4-epimerase; (qualitatively) glucosephosphate isomerase and UDP-N-acetylglucosamine-4-epimerase; (qualitatively, in 10strains) glutamine: fructose-6-phosphate transaminase and (in 6strains) UDP-N-acetylglucosamine synthetase. Most of the mutants were found to contain the enzymes in activities equal to those found in the wild-type strains. These mutants therefore probably have a block involving a transferase. Three mutants were identified to have a defect in UDP-glucose synthetase synthesis. 4 mutants lacked the enzyme UDP-N-acetylglucosamine-4-epimerase. Some of these mutants have an additional block which involves a transferase. In extracts of S. ruiru the enzyme system of Matsuhashi and Strominger which catalyzes the conversion of TDP-glucose to TDP-4-amino-4,6-dideoxyhexose (probably with the configuration of d-galactose), could be identified.
    European Journal of Biochemistry. 03/2005; 1(2):233 - 242.
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    ABSTRACT: A number of lipopolysaccharides derived from Salmonella and Escherichia coli S and R mutant strains were tested for toxicity and anticomplementary activity in the absence of added antiserum. Although all preparations were toxic, only a few exhibited high anticomplementary activity, while others proved to be of low or negligible activity. It was found that isolated lipid A from both active and inactive lipopolysaccharides was strongly anticomplementary as well as toxic, when made water-soluble with the aid of suitable carriers. Treatment of R form lipopoly-saccharide with Mg2+ or Ca2+ led to complete precipitation of the lipopolysaccharide with consequent loss of toxicity and anticomplementary activity. This treatment had practically no effect on the anticomplementary activity and toxicity of S form lipopolysaccharides. When lipopolysaccharide, after reaction with complement, was reisolated and purified, the resulting preparation was found to be non-toxic and of negligible anticomplementary activity. No detectable alterations in either the sugar or the fatty acid composition could be detected. The only significant change was the loss of solubility in water. Treatment of the reisolated lipopolysaccharide with EDTA completely restored solubility in water, toxicity, and anti-complementary activity.
    European Journal of Biochemistry. 03/2005; 19(1):143 - 152.
  • D H Shaw, M J Hart, O Lüderitz
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    ABSTRACT: The core oligosaccharide isolated from the lipopolysaccharide of Aeromonas salmonicida ssp. salmonicida has been investigated by methylation analysis, NMR spectroscopy (13C and 1H), oxidation with periodate and chromium trioxide, and Smith degradation. The following structure is proposed: [Formula: see text]
    Carbohydrate Research 08/1992; 231:83-91. · 2.04 Impact Factor
  • Source
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    ABSTRACT: Biological activities of two groups of synthesized lipid A analogs, the counterpart of biosynthetic precursor, Lehmann's Ia type, 406, and E. coli lipid A type, 506, as well as their non-phosphorylated, and mono-phosphorylated analogs were investigated. The activities employed included four bone marrow cell reactions in mice, mice skin reaction, leukocytes migration in rabbits' cornea, and hemagglutination. Compound 406 and 506 elicited bone marrow reactions in mice and hemagglutination of mouse RBC, although 406 failed to elicit hemorrhage and necrosis also in mice skin. Compound 406 did not elicit corneal reaction in rabbits. The results suggest that for elicitation of this reaction and mice skin reaction, acyloxyacyl structure is required. Cytotoxicity and thromboplastin production of four bone marrow reactions had been reported by us to be endotoxic reactions, since these had not been elicited by peptidoglycan of Lactobacillus and Staphylococcus (1981) and 300 series synthetized analogs (1984) which did not have endotoxic structures. From these results, it seems that these two marrow reactions and hemagglutination require, as does the limulus test, the lipid A part structure as is present in 406.
    Microbiology and Immunology 10/1989; 33(10). · 1.55 Impact Factor
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    ABSTRACT: The S-form lipopolysaccharide of Salmonella abortus equi was separated by a newly elaborated extraction method with organic solvents into three fractions of different chain length of the O-polysaccharide they contained. The three fractions were designated long-chain (20-50 repeating units), short-chain (0-6) and R-fraction (no repeating units) according to their migration pattern in polyacrylamide gel electrophoresis in the presence of sodium dodecylsulphate. The nature of the fractions as long- and short-chain and as R-fraction was confirmed by chemical analysis. The concentration of O-specific sugars was highest in the long-chain fraction, where their molar ratio to glucosamine was ca. 25:1. In the short-chain fraction the ratio of O-sugars to glucosamine was 2.5:1, and in the R-fraction O-specific sugars were absent. The serological properties of the three fractions were in good agreement with their chemical composition.
    Journal of Chromatography A 06/1988; 440:397-404. · 4.61 Impact Factor
  • E Elekes, O Lüderitz, C Galanos, L Bertók
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    ABSTRACT: The chemical composition and the antigenicity of Escherichia coli lipopolysaccharide (LPS) and lipid A were investigated after irradiation with 150 kGy 60Co-gamma ray. Compared to the original preparations, the irradiated LPS showed a significant reduction in glucosamine, glucose and galactose and a decrease in the phosphate content. The fatty acid components were reduced to a smaller degree. Irradiation induced a reduction in the antigenicity of the polysaccharide part. The amount of glucosamine and phosphate decreased in the irradiated lipid A. The fatty acid content was significantly reduced. The alteration in the chemical composition was not paralleled by changes in the antigenicity of irradiated lipid A.
    Acta microbiologica Hungarica 02/1988; 35(3):301-5.
  • Journal of Chromatography A - J CHROMATOGR A. 01/1988; 440:397-404.
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    ABSTRACT: Three enzyme preparations (EIa, EIIa, and EIII), which exhibited fatty acyl esterase activity towards p-nitrophenyl laurate and towards the lipopolysaccharide from Salmonella minnesota R4, were obtained from a cell-free lysate of Acanthamoeba castellanii. In the presence of Triton X-100, EIa and EIIa cleaved all ester-bound fatty acids from the lipopolysaccharide, and EIII cleaved non- and 2-hydroxylated fatty acids, but not ester- (and amide-)bound 3-hydroxymyristic acid. The content of heptose, 3-deoxy-2-octulosonic acid, glucosamine, and phosphate in the degraded preparations was unchanged, although phosphatase and N-acetyl-β-d-glucosaminidase activity was detectable in the enzyme preparations when tested with the respective p-nitrophenyl substrates.
    Carbohydrate Research. 01/1988; 178(1):225-232.
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    ABSTRACT: A pentaacyl precursor of lipid A biosynthesis, termed precursor Ib, and a structural isomer have been chemically synthesized. These compounds were, in comparison to synthetic Escherichia-coli type lipid A or lipopolysaccharide, analyzed for their activity in typical endotoxin test systems. It was found that both precursor Ib and the isomer exhibited similar or only slightly lower pyrogenic, lethal and Shwartzman-phenomenon-inducing activity than lipid A. All preparations were comparable in their B-lymphocyte mitogenicity, macrophage-activating capacity and immunoreactivity towards lipid A antisera. The proton nuclear magnetic resonance spectra of the 1-dephospho derivative of synthetic and bacterial precursor Ib were indistinguishable proving that the previously proposed structure for precursor Ib is correct.
    European Journal of Biochemistry 12/1987; 169(1):27-31. · 3.58 Impact Factor
  • Progress in clinical and biological research 02/1987; 231:25-53.
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    ABSTRACT: A synthetic lipid A (preparation 516), containing seven acyl groups and representing one component of natural free lipid A of Salmonella minnesota R595, has been investigated for biological activity in a number of endotoxin test systems. It was found that the synthetic preparation was, in typical in vivo endotoxin tests (lethality, pyrogenicity, Shwartzman reactivity) as well as in its antigenicity and macrophage activation capacity, significantly less active than natural Salmonella lipid A. However, in other in vitro assay systems (B-cell mitogenicity, complement activation, Limulus amoebocyte lysate gelation) it expressed similar activity as Salmonella lipid A.
    European Journal of Biochemistry 11/1986; 160(1):55-9. · 3.58 Impact Factor

Publication Stats

6k Citations
441.75 Total Impact Points

Institutions

  • 1964–2006
    • Max Planck Institute of Immunobiology and Epigenetics
      Freiburg, Baden-Württemberg, Germany
  • 1978
    • German Cancer Research Center
      Heidelburg, Baden-Württemberg, Germany
  • 1971
    • Washington University in St. Louis
      San Luis, Missouri, United States
  • 1961
    • Roswell Park Cancer Institute
      • Department of Experimental Therapeutics
      Buffalo, New York, United States
  • 1956
    • Universität Heidelberg
      Heidelburg, Baden-Württemberg, Germany