O Lüderitz

CUNY Graduate Center, New York City, New York, United States

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Publications (184)453.27 Total impact

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    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.
    Preview · Article · Jun 2008
  • Otto Westphal · Otto Lüderitz · Erwin Eichenberger · Erwin Neter

    No preview · Chapter · May 2008

  • No preview · Article · Dec 2006 · Annals of the New York Academy of Sciences
  • 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.
    No preview · Article · Jan 2006 · Angewandte Chemie
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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.
    Preview · Article · Mar 2005
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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.
    Preview · Article · Mar 2005
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    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.
    Preview · Article · Mar 2005
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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.
    Preview · Article · Mar 2005
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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.
    Preview · Article · Mar 2005
  • Article: Dedication
    Otto Westphal · Otto Lüderitz

    No preview · Article · Oct 2002 · Acoustics, Speech, and Signal Processing Newsletter, IEEE
  • Derek H. Shaw · M. Jeanne Hart · Otto 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]
    No preview · Article · Aug 1992 · Carbohydrate Research
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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.
    Preview · Article · Oct 1989 · Microbiology and Immunology
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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.
    No preview · Article · Jul 1988 · Carbohydrate Research
  • C Galanos · B H Jiao · T Komuro · M A Freudenberg · O Lüderitz
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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.
    No preview · Article · Jun 1988 · Journal of Chromatography A
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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.
    No preview · Article · May 1988 · Journal of Chromatography A
  • 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.
    No preview · Article · Feb 1988 · Acta microbiologica Hungarica
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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.
    No preview · Article · Dec 1987 · European Journal of Biochemistry

  • No preview · Article · Feb 1987 · Progress in clinical and biological research
  • O. WESTPHAL · O. LÜDERITZ · Ch. GALANOS · H. MAYER · E.Th. RIETSCHEL
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    ABSTRACT: After the introduction of the term bacterial endotoxin early this century by Richard Pfeiffer, about 80 years elapsed until this biologically omnipotent and highly active principle could be chemically clearly defined. Endotoxin was found to reside in the lipopolysaccharide (LPS) of the bacterial cell envelope; it was then pinpointed as the lipid component of LPS, called lipid A. This lipid has an unusual structure - with certain variations on a characteristic backbone - which does not seem to exist anywhere else in nature. After the elucidation of the structure of some lipid A's (E. coli, Salmonella and others) it became more recently possible to identify the pathway of lipid A biosynthesis and to fully synthesize lipid A of E. coli. The synthetic product is chemically, physico-chemically and biologically identical with its natural lipid A prototype. With these achievements the old question as to the structure(s) responsible for endotoxicity has been solved - and a new chapter of research on endotoxin is open. The following review is an extended version of a lecture given by O.W. on May 7, 1985 at the 3rd International Conference on Immunopharmacology in Florence, Italy.
    No preview · Chapter · Dec 1986
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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.
    Preview · Article · Nov 1986 · European Journal of Biochemistry

Publication Stats

10k Citations
453.27 Total Impact Points

Institutions

  • 2008
    • CUNY Graduate Center
      New York City, New York, United States
  • 1966-2005
    • Max Planck Institute of Immunobiology and Epigenetics
      Freiburg, Baden-Württemberg, Germany
  • 1978
    • German Cancer Research Center
      Heidelburg, Baden-Württemberg, Germany
  • 1975
    • University at Buffalo, The State University of New York
      • Department of Oral Biology
      Buffalo, New York, United States
  • 1964-1971
    • Washington University in St. Louis
      San Luis, Missouri, United States
  • 1961
    • Roswell Park Cancer Institute
      • Department of Experimental Therapeutics
      Buffalo, New York, United States