lipid a

Summary

Summary: Lipid A is the biologically active component of lipopolysaccharides. It shows strong endotoxic activity and exhibits immunogenic properties.

Top Publications

  1. pmc Lipid A modification systems in gram-negative bacteria
    Christian R H Raetz
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    Annu Rev Biochem 76:295-329. 2007
  2. ncbi The vaccine adjuvant monophosphoryl lipid A as a TRIF-biased agonist of TLR4
    Veronica Mata-Haro
    Institute for Cellular Therapeutics, University of Louisville, 570 South Preston Street, Louisville, KY 40202, USA
    Science 316:1628-32. 2007
  3. ncbi LPS, TLR4 and infectious disease diversity
    Samuel I Miller
    Department of Medicine, University of Washington Medical School, Seattle, Washington 98195, USA
    Nat Rev Microbiol 3:36-46. 2005
  4. ncbi AS04, an aluminum salt- and TLR4 agonist-based adjuvant system, induces a transient localized innate immune response leading to enhanced adaptive immunity
    Arnaud M Didierlaurent
    GlaxoSmithKline Biologicals, Rixensart, Belgium
    J Immunol 183:6186-97. 2009
  5. pmc Putting endotoxin to work for us: monophosphoryl lipid A as a safe and effective vaccine adjuvant
    C R Casella
    Institute for Cellular Therapeutics, University of Louisville School of Medicine, Louisville, KY, 40202, USA
    Cell Mol Life Sci 65:3231-40. 2008
  6. pmc Ehrlichia chaffeensis and Anaplasma phagocytophilum lack genes for lipid A biosynthesis and incorporate cholesterol for their survival
    Mingqun Lin
    Department of Veterinary Biosciences, The Ohio State University, Columbus, Ohio 43210, USA
    Infect Immun 71:5324-31. 2003
  7. ncbi GlaxoSmithKline Adjuvant Systems in vaccines: concepts, achievements and perspectives
    Nathalie Garçon
    GlaxoSmithKline Biologicals, Research and Development, 1330 Rixensart, Belgium
    Expert Rev Vaccines 6:723-39. 2007
  8. ncbi Enhanced humoral and memory B cellular immunity using HPV16/18 L1 VLP vaccine formulated with the MPL/aluminium salt combination (AS04) compared to aluminium salt only
    Sandra L Giannini
    Research and Development, GlaxoSmithKline Biologicals, Rue de l Institut 89, 1330 Rixensart, Belgium
    Vaccine 24:5937-49. 2006
  9. pmc Porphyromonas gingivalis lipopolysaccharide contains multiple lipid A species that functionally interact with both toll-like receptors 2 and 4
    Richard P Darveau
    Department of Periodontics, University of Washington, Health Sciences Center, Box 357444, Seattle, WA 98195, USA
    Infect Immun 72:5041-51. 2004
  10. ncbi Essential role of MD-2 in LPS responsiveness and TLR4 distribution
    Yoshinori Nagai
    Division of Infectious Genetics, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
    Nat Immunol 3:667-72. 2002

Detail Information

Publications354 found, 100 shown here

  1. pmc Lipid A modification systems in gram-negative bacteria
    Christian R H Raetz
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    Annu Rev Biochem 76:295-329. 2007
    The lipid A moiety of lipopolysaccharide forms the outer monolayer of the outer membrane of most gram-negative bacteria...
  2. ncbi The vaccine adjuvant monophosphoryl lipid A as a TRIF-biased agonist of TLR4
    Veronica Mata-Haro
    Institute for Cellular Therapeutics, University of Louisville, 570 South Preston Street, Louisville, KY 40202, USA
    Science 316:1628-32. 2007
    ..Monophosphoryl lipid A (MPLA) is a low-toxicity derivative of LPS with useful immunostimulatory properties, which is nearing regulatory ..
  3. ncbi LPS, TLR4 and infectious disease diversity
    Samuel I Miller
    Department of Medicine, University of Washington Medical School, Seattle, Washington 98195, USA
    Nat Rev Microbiol 3:36-46. 2005
    ..This review will examine the hypothesis that the variability of bacterial ligands such as LPS and their innate immune receptors is an important factor in determining the outcome of infectious disease...
  4. ncbi AS04, an aluminum salt- and TLR4 agonist-based adjuvant system, induces a transient localized innate immune response leading to enhanced adaptive immunity
    Arnaud M Didierlaurent
    GlaxoSmithKline Biologicals, Rixensart, Belgium
    J Immunol 183:6186-97. 2009
    Adjuvant System 04 (AS04) combines the TLR4 agonist MPL (3-O-desacyl-4'-monophosphoryl lipid A) and aluminum salt. It is a new generation TLR-based adjuvant licensed for use in human vaccines...
  5. pmc Putting endotoxin to work for us: monophosphoryl lipid A as a safe and effective vaccine adjuvant
    C R Casella
    Institute for Cellular Therapeutics, University of Louisville School of Medicine, Louisville, KY, 40202, USA
    Cell Mol Life Sci 65:3231-40. 2008
    ..The vaccine adjuvant monophosphoryl lipid A is a detoxified form of the endotoxin lipopolysaccharide, and is among the first of a new generation of Toll-like ..
  6. pmc Ehrlichia chaffeensis and Anaplasma phagocytophilum lack genes for lipid A biosynthesis and incorporate cholesterol for their survival
    Mingqun Lin
    Department of Veterinary Biosciences, The Ohio State University, Columbus, Ohio 43210, USA
    Infect Immun 71:5324-31. 2003
    ..phagocytophilum genome sequences revealed that these bacteria lack all genes for the biosynthesis of lipid A and most genes for the biosynthesis of peptidoglycan, which confer structural strength to gram-negative bacteria...
  7. ncbi GlaxoSmithKline Adjuvant Systems in vaccines: concepts, achievements and perspectives
    Nathalie Garçon
    GlaxoSmithKline Biologicals, Research and Development, 1330 Rixensart, Belgium
    Expert Rev Vaccines 6:723-39. 2007
    ..Altogether, the promising clinical results strongly support the concept of Adjuvant Systems and allow for further development of new vaccines, best adapted to the target population and the immune mechanisms of protection...
  8. ncbi Enhanced humoral and memory B cellular immunity using HPV16/18 L1 VLP vaccine formulated with the MPL/aluminium salt combination (AS04) compared to aluminium salt only
    Sandra L Giannini
    Research and Development, GlaxoSmithKline Biologicals, Rue de l Institut 89, 1330 Rixensart, Belgium
    Vaccine 24:5937-49. 2006
    ..the ability of an HPV16/18 L1 VLP vaccine formulated with the AS04 adjuvant system (3-O-desacyl-4'-monophosphoryl lipid A (MPL) and aluminium salt) to induce an immune response of higher magnitude and persistence compared to a vaccine ..
  9. pmc Porphyromonas gingivalis lipopolysaccharide contains multiple lipid A species that functionally interact with both toll-like receptors 2 and 4
    Richard P Darveau
    Department of Periodontics, University of Washington, Health Sciences Center, Box 357444, Seattle, WA 98195, USA
    Infect Immun 72:5041-51. 2004
    ..In this report it is shown that P. gingivalis LPS is highly heterogeneous, containing more lipid A species than previously described...
  10. ncbi Essential role of MD-2 in LPS responsiveness and TLR4 distribution
    Yoshinori Nagai
    Division of Infectious Genetics, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
    Nat Immunol 3:667-72. 2002
    ..Thus, MD-2 is essential for correct intracellular distribution and LPS-recognition of TLR4...
  11. ncbi Lipopolysaccharide: Biosynthetic pathway and structure modification
    Xiaoyuan Wang
    State Key Laboratory of Food Science and Technology, Jiangnan University, 1800 Lihu Avenue, Wuxi 214122, China
    Prog Lipid Res 49:97-107. 2010
    ..It is comprised of a hydrophilic polysaccharide and a hydrophobic component referred to as lipid A. Lipid A is responsible for the major bioactivity of endotoxin, and is recognized by immune cells as a pathogen-..
  12. pmc Leish-111f, a recombinant polyprotein vaccine that protects against visceral Leishmaniasis by elicitation of CD4+ T cells
    Rhea N Coler
    Infectious Disease Research Institute, 1124 Columbia St, Suite 400, Seattle, WA 98104, USA
    Infect Immun 75:4648-54. 2007
    ..We evaluated the immune response and protection induced by Leish-111f formulated with monophosphoryl lipid A in a stable emulsion (Leish-111f+MPL-SE) and demonstrated that mice developed strong humoral and T-cell responses ..
  13. pmc Development and characterization of synthetic glucopyranosyl lipid adjuvant system as a vaccine adjuvant
    Rhea N Coler
    Preclinical Biology, Infectious Disease Research Institute, Seattle, Washington, United States of America
    PLoS ONE 6:e16333. 2011
    ..We report here on the characterization of a synthetic hexaacylated lipid A derivative, denoted as glucopyranosyl lipid adjuvant (GLA)...
  14. ncbi Human Toll-like receptor 4 recognizes host-specific LPS modifications
    Adeline M Hajjar
    Department of Immunology, University of Washington, Seattle, WA 98195, USA
    Nat Immunol 3:354-9. 2002
    ..Thus, in contrast to mice, humans use TLR4 to recognize a molecular signature of bacterial-host adaptation to modulate the innate immune response...
  15. pmc Hemin-dependent modulation of the lipid A structure of Porphyromonas gingivalis lipopolysaccharide
    Montaser N Al-Qutub
    Department of Periodontics, University of Washington, Box 357444, Seattle, Washington 98195, USA
    Infect Immun 74:4474-85. 2006
    ..P. gingivalis lipopolysaccharide (LPS) displays a significant amount of lipid A structural heterogeneity, containing both penta- and tetra-acylated lipid A structures...
  16. ncbi Allergen-specific immunotherapy with a monophosphoryl lipid A-adjuvanted vaccine: reduced seasonally boosted immunoglobulin E production and inhibition of basophil histamine release by therapy-induced blocking antibodies
    N Mothes
    Department of Pathophysiology, Vienna General Hospital, University of Vienna, Vienna, Austria
    Clin Exp Allergy 33:1198-208. 2003
    ..The allergen extract-based analyses of immunotherapy-induced effects yielded highly controversial results regarding a beneficial role of therapy-induced IgG antibodies...
  17. pmc Tetra- and penta-acylated lipid A structures of Porphyromonas gingivalis LPS differentially activate TLR4-mediated NF-κB signal transduction cascade and immuno-inflammatory response in human gingival fibroblasts
    Thanuja D K Herath
    Faculty of Dentistry, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
    PLoS ONE 8:e58496. 2013
    ..Lipopolysaccharides (LPS), as a key virulent attribute of P. gingivalis, possesses significant amount of lipid A heterogeneity containing tetra- (LPS1435/1449) and penta-acylated (LPS1690) structures...
  18. ncbi Crystal structures of human MD-2 and its complex with antiendotoxic lipid IVa
    Umeharu Ohto
    Graduate School of Pharmaceutical Sciences, University of Tokyo, 7 3 1 Hongo, Bunkyo ku, Tokyo 113 0033, Japan
    Science 316:1632-4. 2007
    ..Crystal structures of human MD-2 and its complex with the antiendotoxic tetra-acylated lipid A core of LPS have been determined at 2.0 and 2.2 angstrom resolutions, respectively...
  19. pmc Role of lipid A acylation in Yersinia enterocolitica virulence
    Camino Pérez-Gutiérrez
    Fundación Caubet CIMERA Illes Balears, 07110 Bunyola, Spain
    Infect Immun 78:2768-81. 2010
    ..Here, we report that Y. enterocolitica 8081 serotype O:8 synthesized tetra-acylated lipid A at 37 degrees C but that hexa-acylated lipid A predominated at 21 degrees C...
  20. ncbi Structure and function of lipopolysaccharides
    Clett Erridge
    Medical Microbiology, University of Edinburgh Medical School, Edinburgh, Scotland, EH8 9AG, UK
    Microbes Infect 4:837-51. 2002
    ..Consideration is given in this review to the relationship between structure and function of these lipopolysaccharides...
  21. pmc Modification of the structure and activity of lipid A in Yersinia pestis lipopolysaccharide by growth temperature
    Kazuyoshi Kawahara
    Department of Bacteriology, The Kitasato Institute, Tokyo 108 8642, Japan
    Infect Immun 70:4092-8. 2002
    Yersinia pestis strain Yreka was grown at 27 or 37 degrees C, and the lipid A structures (lipid A-27 degrees C and lipid A-37 degrees C) of the respective lipopolysaccharides (LPS) were investigated by matrix-assisted laser desorption ..
  22. pmc Single and combination herpes simplex virus type 2 glycoprotein vaccines adjuvanted with CpG oligodeoxynucleotides or monophosphoryl lipid A exhibit differential immunity that is not correlated to protection in animal models
    Tansi Khodai
    Internal Medicine Research Unit, Pfizer Research and Development, Sandwich, UK
    Clin Vaccine Immunol 18:1702-9. 2011
    ..was the GlaxoSmithKline (GSK) subunit vaccine based on the glycoprotein gD with the adjuvant monophosphoryl lipid A (MPL)...
  23. ncbi Lipid A structure of Pseudoalteromonas haloplanktis TAC 125: use of electrospray ionization tandem mass spectrometry for the determination of fatty acid distribution
    Maria Michela Corsaro
    Dipartimento di Chimica Organica e Biochimica, Universita di Napoli Federico II, Complesso Universitario Monte S Angelo, Via Cynthia 4, 80126 Naples, Italy
    J Mass Spectrom 37:481-8. 2002
    The use of electrospray Ionization (ESI) tandem mass spectrometry (MS/MS) for the structural determination of the lipid A components of the psychrophilic bacterium Pseudoalteromonas haloplanktis TAC 125 is reported...
  24. pmc Identification of undecaprenyl phosphate-beta-D-galactosamine in Francisella novicida and its function in lipid A modification
    Xiaoyuan Wang
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    Biochemistry 48:1162-72. 2009
    Francisella tularensis is a highly infectious pathogen that causes tularemia. Francisella lipid A contains an unusual galactosamine (GalN) unit, attached to its 1-phosphate moiety...
  25. ncbi Evaluation of protective effect of recombinant dense granule antigens GRA2 and GRA6 formulated in monophosphoryl lipid A (MPL) adjuvant against Toxoplasma chronic infection in mice
    Majid Golkar
    CNRS UMR 5163 Université Joseph Fourier, UFR de Biologie, Institut Jean Roget, Campus Sante, Domaine de la Merci BP 170, 38042 Grenoble Cedex 09, France
    Vaccine 25:4301-11. 2007
    ..This study shows the protective efficacy of recombinant GRA2 against chronic infection by T. gondii and confirms the utility of MPL adjuvant in enabling a vaccine candidate to induce a protective Th1 immune response...
  26. ncbi Two msbB genes encoding maximal acylation of lipid A are required for invasive Shigella flexneri to mediate inflammatory rupture and destruction of the intestinal epithelium
    Hélène d'Hauteville
    Unité de Pathogénie Microbienne Moléculaire and Institut National de la Santé et de la Recherche Médicale, Unité 389, Institut Pasteur, 28 rue du Docteur Roux, 75724 Paris Cedex 15, France
    J Immunol 168:5240-51. 2002
    ..However, the respective role of this invasive phenotype and of lipid A, the endotoxin of the Shigella LPS, in eliciting the inflammatory cascade that leads to rupture and destruction ..
  27. ncbi Human TLR4 polymorphism D299G/T399I alters TLR4/MD-2 conformation and response to a weak ligand monophosphoryl lipid A
    Natsuko Yamakawa
    Division of Innate Immunity, The Institute of Medical Science, University of Tokyo, 4 6 1 Shirokanedai, Tokyo 108 8639, Japan
    Int Immunol 25:45-52. 2013
    ..of TLR4/MD-2, ligand-dependent TLR4/MD-2 dimerization or TLR4/MD-2 responses to a weak agonist monophosphoryl lipid A (MPL)...
  28. pmc Genetic and functional analysis of a PmrA-PmrB-regulated locus necessary for lipopolysaccharide modification, antimicrobial peptide resistance, and oral virulence of Salmonella enterica serovar typhimurium
    J S Gunn
    Department of Microbiology, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229, USA
    Infect Immun 68:6139-46. 2000
    ..Both pmrE and pmrHFIJKLM produce products required for the biosynthesis of lipid A with 4-aminoarabinose (Ara4N)...
  29. pmc MyD88-dependent SHIP1 regulates proinflammatory signaling pathways in dendritic cells after monophosphoryl lipid A stimulation of TLR4
    Caglar Cekic
    Department of Microbiology and Immunology, University of Louisville School of Medicine, Louisville, KY 40202, USA
    J Immunol 186:3858-65. 2011
    We previously showed that monophosphoryl lipid A (MLA) activates TLR4 in dendritic cells (DCs) in a Toll/IL-1R domain-containing adaptor inducing IFN-β (TRIF)-biased manner: MLA produced from Salmonella minnesota Re595 induced signaling ..
  30. pmc Vaccine adjuvants aluminum and monophosphoryl lipid A provide distinct signals to generate protective cytotoxic memory CD8 T cells
    Megan K L Macleod
    The Howard Hughes Medical Institute and Integrated Department of Immunology, National Jewish Health, Denver, CO 80206, USA
    Proc Natl Acad Sci U S A 108:7914-9. 2011
    ..cytotoxic T-cell differentiation occurred only in the presence of an additional adjuvant, monophosphoryl lipid A (MPL). MPL-induced IL-6 was required for cytotoxic differentiation...
  31. pmc MsbA transporter-dependent lipid A 1-dephosphorylation on the periplasmic surface of the inner membrane: topography of francisella novicida LpxE expressed in Escherichia coli
    Xiaoyuan Wang
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 279:49470-8. 2004
    The lipid A anchor of Francisella tularensis lipopolysaccharide (LPS) lacks both phosphate groups present in Escherichia coli lipid A. Membranes of Francisella novicida (an environmental strain related to F...
  32. pmc Phosphoryl moieties of lipid A from Neisseria meningitidis and N. gonorrhoeae lipooligosaccharides play an important role in activation of both MyD88- and TRIF-dependent TLR4-MD-2 signaling pathways
    Mingfeng Liu
    Center for Immunochemistry, Veterans Affairs Medical Center, San Francisco, CA, 94121, USA
    J Immunol 185:6974-84. 2010
    ..ion abundances in MALDI-TOF mass spectrometry that are indicative of the number of phosphoryl substituents on the lipid A (LA) component of the LOS...
  33. pmc Differential activation of human TLR4 by Escherichia coli and Shigella flexneri 2a lipopolysaccharide: combined effects of lipid A acylation state and TLR4 polymorphisms on signaling
    Prasad Rallabhandi
    Department of Microbiology and Immunology, Center for Vaccine Development, University of Maryland, Baltimore 21201, USA
    J Immunol 180:1139-47. 2008
    The lipid A of LPS activates TLR4 through an interaction with myeloid differentiation protein-2 (MD-2) and the degree of lipid A acylation affects TLR4 responsiveness...
  34. ncbi Pseudomonas aeruginosa lipid A diversity and its recognition by Toll-like receptor 4
    Robert K Ernst
    Department of Medicine, HSB K 155, Box 357710, University of Washington, Seattle, WA 98195, USA
    J Endotoxin Res 9:395-400. 2003
    b>Lipid A is the pro-inflammatory component of bacterial lipopolysaccharide, the major surface component of Gram-negative bacteria...
  35. ncbi Diversity of endotoxin and its impact on pathogenesis
    M Stephen Trent
    Department of Microbiology, James H Quillen College of Medicine, East Tennessee State University, Johnson City, USA
    J Endotoxin Res 12:205-23. 2006
    ..The LPS of a number of bacteria is composed of three distinct regions--lipid A, a short core oligosaccharide, and the O-antigen polysaccharide...
  36. pmc Modification of lipid A biosynthesis in Neisseria meningitidis lpxL mutants: influence on lipopolysaccharide structure, toxicity, and adjuvant activity
    P van der Ley
    Laboratories of Vaccine Research, National Institute of Public Health and the Environment, RIVM, 3720 BA Bilthoven, The Netherlands
    Infect Immun 69:5981-90. 2001
    ..Two genes homologous to lpxL and lpxM from Escherichia coli and other gram-negative bacteria, which are involved in lipid A acyloxyacylation, were identified in Neisseria meningitidis strain H44/76 and insertionally inactivated...
  37. pmc Applying TLR synergy in immunotherapy: implications in cutaneous leishmaniasis
    Vanitha S Raman
    Infectious Disease Research Institute, Seattle, WA 98104, USA
    J Immunol 185:1701-10. 2010
    ..L110f, a well-established Leishmania poly-protein vaccine candidate, in conjunction with either monophosphoryl lipid A, a TLR4 agonist, or CpG, a TLR9 agonist, or a combination of these, and evaluated anti-Leishmania immune ..
  38. ncbi PmrA-PmrB-regulated genes necessary for 4-aminoarabinose lipid A modification and polymyxin resistance
    J S Gunn
    University of Washington, Department of Medicine, Seattle 98195, USA
    Mol Microbiol 27:1171-82. 1998
    ..resistance is encoded by the PmrA-PmrB regulon, whose products modify the lipopolysaccharide (LPS) core and lipid A regions with ethanolamine and add aminoarabinose to the 4' phosphate of lipid A. Two PmrA-PmrB-regulated S...
  39. pmc Phosphoethanolamine modification of lipid A in colistin-resistant variants of Acinetobacter baumannii mediated by the pmrAB two-component regulatory system
    Alejandro Beceiro
    Health Protection Agency, Microbiology Services Colindale, London, United Kingdom
    Antimicrob Agents Chemother 55:3370-9. 2011
    ..of flight (MALDI-TOF) mass spectrometry showed the addition of phosphoethanolamine to the hepta-acylated form of lipid A in the resistant variants and in strain ATCC 19606 grown under low-Mg(2+) induction conditions...
  40. pmc Phosphoethanolamine substitution of lipid A and resistance of Neisseria gonorrhoeae to cationic antimicrobial peptides and complement-mediated killing by normal human serum
    Lisa A Lewis
    Department of Medicine, University of Massachusetts School of Medicine, Worcester, Massachusetts, USA
    Infect Immun 77:1112-20. 2009
    ..However, loss of phosphoethanolamine substitution from the lipid A component of lipooligosaccharide, due to insertional inactivation of lptA, resulted in increased gonococcal ..
  41. pmc Structural characterization of the lipid A component of Helicobacter pylori rough- and smooth-form lipopolysaccharides
    A P Moran
    Department of Microbiology, University College, Galway, Ireland
    J Bacteriol 179:6453-63. 1997
    The chemical structure of free lipid A isolated from rough- and smooth-form lipopolysaccharides (R-LPS and S-LPS, respectively) of the human gastroduodenal pathogen Helicobacter pylori was elucidated by compositional and degradative ..
  42. pmc Naturally occurring lipid A mutants in neisseria meningitidis from patients with invasive meningococcal disease are associated with reduced coagulopathy
    Floris Fransen
    Laboratory of Vaccine Research, Netherlands Vaccine Institute, Bilthoven, The Netherlands
    PLoS Pathog 5:e1000396. 2009
    ..TLR4 recognizes the lipid A moiety of the LPS molecule, and the chemical composition of the lipid A determines how well it is recognized by ..
  43. pmc Phosphorylation of the lipid A region of meningococcal lipopolysaccharide: identification of a family of transferases that add phosphoethanolamine to lipopolysaccharide
    Andrew D Cox
    Institute for Biological Sciences, National Research Council, Ottawa, Ontario K1A 0R6, Canada
    J Bacteriol 185:3270-7. 2003
    ..meningitidis elaborated lipopolysaccharide (LPS) containing a lipid A that was characteristically phosphorylated with multiple phosphate and phosphoethanolamine residues...
  44. pmc Differential induction of innate immune responses by synthetic lipid a derivatives
    Jidnyasa Gaekwad
    Complex Carbohydrate Research Center, University of Georgia, Athens, Georgia 30602, USA
    J Biol Chem 285:29375-86. 2010
    ..Heterogeneity in the structure of lipid A (the active component of LPS) and possible contaminations with other inflammatory components have made it ..
  45. pmc Activation of Toll-like receptors by Burkholderia pseudomallei
    T Eoin West
    Department of Medicine, University of Washington, Seattle, Washington, USA
    BMC Immunol 9:46. 2008
    ..We examined TLR signaling induced by B. pseudomallei, B. pseudomallei LPS, and B. pseudomallei lipid A using gain-of-function transfection assays of NF-kappaB activation and studies of TLR-deficient macrophages.
  46. pmc Human Toll-like receptor 4 responses to P. gingivalis are regulated by lipid A 1- and 4'-phosphatase activities
    Stephen R Coats
    Department of Periodontics, School of Dentistry, University of Washington, 1959 NE Pacific St, Seattle, WA 98195 7444, USA
    Cell Microbiol 11:1587-99. 2009
    ..We show that the oral pathogen, Porphyromonas gingivalis, uses endogenous lipid A 1- and 4'-phosphatase activities to modify its LPS, creating immunologically silent, non-phosphorylated lipid A...
  47. pmc An msbB homologue carried in plasmid pO157 encodes an acyltransferase involved in lipid A biosynthesis in Escherichia coli O157:H7
    Sang Hyun Kim
    Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada N1G 2W1
    Infect Immun 72:1174-80. 2004
    ..The msbB double-mutant strain generated pentaacyl lipid A, while the single-mutant strains synthesized hexaacyl lipid A...
  48. pmc An outer membrane enzyme encoded by Salmonella typhimurium lpxR that removes the 3'-acyloxyacyl moiety of lipid A
    C Michael Reynolds
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 281:21974-87. 2006
    The Salmonella and related bacteria modify the structure of the lipid A portion of their lipopolysaccharide in response to environmental stimuli...
  49. ncbi Lipid A receptor TLR4-mediated signaling pathways
    Masahiro Yamamoto
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka 565 0871, Japan
    Adv Exp Med Biol 667:59-68. 2010
    b>Lipid A is a strong activator of monocytes to release immune stimulators such as proinflammatory cytokines...
  50. pmc Temperature-dependent modulation of Porphyromonas gingivalis lipid A structure and interaction with the innate host defenses
    Michael A Curtis
    Centre for Immunology and Infectious Disease, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London E1 2AT, United Kingdom
    Infect Immun 79:1187-93. 2011
    b>Lipid A structure is a critical determinant of the interaction between pathogens and the innate immune system...
  51. ncbi Differential modulation of human {beta}-defensins expression in human gingival epithelia by Porphyromonas gingivalis lipopolysaccharide with tetra- and penta-acylated lipid A structures
    Qian Lu
    The University of Hong Kong, Prince Philip Dental Hospital, Hong Kong
    Innate Immun 15:325-35. 2009
    ..It displays a significant amount of lipid A structural heterogeneity, containing both tetra- (LPS(1435/1449) ) and penta-acylated (LPS( 1690)) lipid A ..
  52. ncbi Redefining the requisite lipopolysaccharide structure in Escherichia coli
    Timothy C Meredith
    Department of Medicinal Chemistry, College of Pharmacy, University of Michigan, 428 Church Street, Ann Arbor, Michigan 48109 1065, USA
    ACS Chem Biol 1:33-42. 2006
    ..LPS structure required for growth of Escherichia coli has long been recognized as two Kdo residues attached to lipid A, inextricably linking viability to toxicity...
  53. pmc Substitution of the Bordetella pertussis lipid A phosphate groups with glucosamine is required for robust NF-kappaB activation and release of proinflammatory cytokines in cells expressing human but not murine Toll-like receptor 4-MD-2-CD14
    Nico Marr
    Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada
    Infect Immun 78:2060-9. 2010
    Bordetella pertussis endotoxin is a key modulator of the host immune response, mainly due to the role of its lipid A moiety in Toll-like receptor 4 (TLR4)-mediated signaling...
  54. ncbi Structural analysis of Francisella tularensis lipopolysaccharide
    Evgeny Vinogradov
    Institute for Biological Sciences, National Research Council, Ottawa, Canada
    Eur J Biochem 269:6112-8. 2002
    The structure of the lipid A and core region of the lipopolysaccharide (LPS) from Francisella tularensis (ATCC 29684) was analysed using NMR, mass spectrometry and chemical methods...
  55. ncbi Does the shape of lipid A determine the interaction of LPS with Toll-like receptors?
    Mihai G Netea
    Dept of Medicine, Division of General Internal Medicine, University Medical Center St Radboud, Geert Grooteplein 8, PO Box 9101, 6500 HB, Nijmegen, The Netherlands
    Trends Immunol 23:135-9. 2002
    ..It has been proposed that the shape of the lipid A component determines the bioactivity of LPS, with lipid A that adopts a conical conformation being more active ..
  56. pmc MD-2-mediated ionic interactions between lipid A and TLR4 are essential for receptor activation
    Jianmin Meng
    Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
    J Biol Chem 285:8695-702. 2010
    ..MD-2 complexes to activate intracellular signaling. However, exactly how lipid A, the endotoxic moiety of LPS, activates myeloid lineage cells remains unknown...
  57. ncbi Effect of cold shock on lipid A biosynthesis in Escherichia coli. Induction At 12 degrees C of an acyltransferase specific for palmitoleoyl-acyl carrier protein
    S M Carty
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 274:9677-85. 1999
    Palmitoleate is not present in lipid A isolated from Escherichia coli grown at 30 degrees C or higher, but it comprises approximately 11% of the fatty acyl chains of lipid A in cells grown at 12 degrees C...
  58. pmc Immunogenicity and protective capacity of a virosomal respiratory syncytial virus vaccine adjuvanted with monophosphoryl lipid A in mice
    Tobias Kamphuis
    Department of Medical Microbiology, Molecular Virology Section, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
    PLoS ONE 7:e36812. 2012
    ..As a new approach, we used reconstituted RSV viral envelopes, i.e. virosomes, with incorporated monophosphoryl lipid A (MPLA) adjuvant to enhance immunogenicity and to skew the immune response towards a Th1 phenotype...
  59. ncbi Function of the htrB high temperature requirement gene of Escherichia coli in the acylation of lipid A: HtrB catalyzed incorporation of laurate
    T Clementz
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 271:12095-102. 1996
    ..of overexpressing the lauroyl transferase that functions after 3-deoxy-D-manno-octulosonic acid (Kdo) addition in lipid A biosynthesis (Brozek, K. A., and Raetz, C. R. H. (1990) J. Biol. Chem. 265, 15410-15417). The E...
  60. pmc Analysis of the networks controlling the antimicrobial-peptide-dependent induction of Klebsiella pneumoniae virulence factors
    Enrique Llobet
    Laboratory Microbial Pathogenesis, Fundació d Investigació Sanitària de les Illes Balears, Recinto Hospital Joan March, Carretera Soller km 12, 07110 Bunyola, Spain
    Infect Immun 79:3718-32. 2011
    ..treatment upregulates the expression of the capsule polysaccharide operon and the loci required to modify the lipid A with aminoarabinose and palmitate with a concomitant increase in capsule and lipid A species containing such ..
  61. pmc Toll-like receptor 4 stimulation with the detoxified ligand monophosphoryl lipid A improves Alzheimer's disease-related pathology
    Jean Philippe Michaud
    Neuroscience Laboratory, Department of Molecular Medicine, Centre Hospitalier Universitaire de Quebec Research Center, Laval University, Quebec City, QC, Canada G1V 4G2
    Proc Natl Acad Sci U S A 110:1941-6. 2013
    ..Monophosphoryl lipid A (MPL) is an LPS-derived Toll-like receptor 4 agonist that exhibits unique immunomodulatory properties at doses ..
  62. ncbi The safety evaluation of adjuvants during vaccine development: the AS04 experience
    Nathalie Garçon
    GlaxoSmithKline Biologicals, Avenue Fleming, 20, 1300 Wavre, Belgium
    Vaccine 29:4453-9. 2011
    ..We also discuss how the knowledge of adjuvant mode of action can support the current practice of safety evaluation...
  63. pmc ATF3 plays a key role in Kdo2-lipid A-induced TLR4-dependent gene expression via NF-κB activation
    Eun Young Kim
    Department of Molecular Science and Technology, Ajou University, Suwon, Korea
    PLoS ONE 5:e14181. 2010
    ..This study addresses the role of ATF3 in the Kdo(2)-Lipid A-induced Toll-like receptor 4 (TLR4) signaling pathway in mouse embryonic fibroblasts (MEF)...
  64. pmc Selective TRIF-dependent signaling by a synthetic toll-like receptor 4 agonist
    William S Bowen
    GlaxoSmithKline Biologicals, 553 Old Corvallis Road, Hamilton, MT 59840, USA
    Sci Signal 5:ra13. 2012
    ..and vaccine adjuvant CRX-547, a member of the aminoalkyl glucosaminide 4-phosphate (AGP) class of synthetic lipid A mimetics, displayed TRIF-selective signaling in human cells, which was dependent on a minor structural ..
  65. ncbi Sublingual allergen-specific immunotherapy adjuvanted with monophosphoryl lipid A: a phase I/IIa study
    Oliver Pfaar
    Department of Otorhinolaryngology, University Hospital Mannheim, Center for Rhinology and Allergology, Wiesbaden, Germany
    Int Arch Allergy Immunol 154:336-44. 2011
    ..This study assessed the effects of the Toll-like receptor 4 agonist monophosphoryl lipid A (MPL®) on safety/tolerability and clinical and immunological efficacy when combined with grass pollen SLIT ..
  66. pmc Lipopolysaccharide and monophosphoryl lipid A differentially regulate interleukin-12, gamma interferon, and interleukin-10 mRNA production in murine macrophages
    C A Salkowski
    Department of Microbiology and Immunology, Uniformed Services, University of the Health Sciences, Bethesda, Maryland 20814, USA
    Infect Immun 65:3239-47. 1997
    Monophosphoryl lipid A (MPL) is a nontoxic derivative of the lipid A region of lipopolysaccharide (LPS) that is being developed as both an adjuvant and prophylactic drug for septic shock...
  67. ncbi Chemical structure of lipid A from Helicobacter pylori strain 206-1 lipopolysaccharide
    Y Suda
    Department of Chemistry, Graduate School of Science, Osaka University, Toyonaka
    J Biochem 121:1129-33. 1997
    The chemical structure of a novel lipid A, which was obtained as a major component from lipopolysaccharide of Helicobacter pylori strain 206-1, was determined to be a glucosamine beta(1-6) disaccharide 1-(2-aminoethyl)phosphate acylated ..
  68. ncbi Lipid A receptor TLR4-mediated signaling pathways
    Masahiro Yamamoto
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan
    Adv Exp Med Biol 667:59-68. 2009
    ..In recent years, Lipid Ahas also been recognized by a Toll-like receptor, TLR4. Activation of TLR4 by LPS or Lipid A triggers signal transduction via the cytoplasmic domain called the Toll/IL-1 Receptor (TIR) domain...
  69. pmc Toll-like receptor 4-dependent recognition of structurally different forms of chemically synthesized lipid As of Porphyromonas gingivalis
    N Sawada
    Department of Oral Microbiology, Asahi University School of Dentistry, Gifu, Japan
    Clin Exp Immunol 148:529-36. 2007
    ..gingivalis is shown to be unusual because the LPS contains a greater number of lipid A species, such as tri-, tetra-, and/or penta-acylated lipid As...
  70. pmc MD-2 residues tyrosine 42, arginine 69, aspartic acid 122, and leucine 125 provide species specificity for lipid IVA
    Jianmin Meng
    Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
    J Biol Chem 285:27935-43. 2010
    ..MD-2 complex. A synthetic lipid A precursor, lipid IV(A), induces an innate immune response in mice but not in humans...
  71. ncbi Porphyromonas gingivalis lipopolysaccharide lipid A heterogeneity differentially modulates the expression of IL-6 and IL-8 in human gingival fibroblasts
    Thanuja D K Herath
    Faculty of Dentistry, The University of Hong Kong, Hong Kong SAR, China
    J Clin Periodontol 38:694-701. 2011
    ..amount of structural heterogeneity, containing both tetra- (LPS(1435/1449) ) and penta-acylated (LPS(1690) ) lipid A structures. This study investigated the effects of the two isoforms of P...
  72. ncbi Monophosphoryl lipid A adjuvant reverses a principal histologic parameter of formalin-inactivated respiratory syncytial virus vaccine-induced disease
    G A Prince
    Virion Systems Inc, Rockville, MD 20850, USA
    Vaccine 19:2048-54. 2001
    ..that immunization with formalin-inactivated vaccine formulated with the adjuvant, 3-deacylated monophosphoryl lipid A, dramatically reduces or eliminates the polymorphonuclear leukocyte infiltration within the alveoli of cotton ..
  73. ncbi Micromethods for the characterization of lipid A-core and O-antigen lipopolysaccharide
    Cristina L Marolda
    Department of Microbiology and Immunology, University of Western Ontario, London, Ontario, Canada
    Methods Mol Biol 347:237-52. 2006
    ..This chapter describes a collection of methods routinely used in our laboratory for the characterization of LPS in Escherichia coli and other bacteria...
  74. ncbi Biological properties of the native and synthetic lipid A of Porphyromonas gingivalis lipopolysaccharide
    H Kumada
    Department of Oral Microbiology, Kanagawa Dental College, Yokosuka, Kanagawa, Japan
    Oral Microbiol Immunol 23:60-9. 2008
    A pentaacyl and diphosphoryl lipid A molecule found in the lipid A isolated from Porphyromonas gingivalis lipopolysaccharide (LPS) was chemically synthesized, and its characteristics were evaluated to reconfirm its interesting ..
  75. ncbi Removal of phosphate from lipid A as a strategy to detoxify lipopolysaccharide
    Hafida Bentala
    Groningen University Institute for Drug Exploration GUIDE, Department of Pharmacokinetics and Drug Delivery, University of Groningen, The Netherlands
    Shock 18:561-6. 2002
    ..The toxic moiety of LPS is the well-preserved lipid A part...
  76. ncbi Analysis of adverse events of potential autoimmune aetiology in a large integrated safety database of AS04 adjuvanted vaccines
    Thomas Verstraeten
    GlaxoSmithKline Biologicals, Rixensart, Belgium
    Vaccine 26:6630-8. 2008
    ..herpes simplex virus (HSV), contain a novel Adjuvant System, AS04, composed of 3-O-desacyl-4' monophosphoryl lipid A and aluminium salts...
  77. pmc Pseudomonas aeruginosa exploits lipid A and muropeptides modification as a strategy to lower innate immunity during cystic fibrosis lung infection
    Cristina Cigana
    Infection and Cystic Fibrosis Unit, San Raffaele Scientific Institute, Milano, Italy
    PLoS ONE 4:e8439. 2009
    ..5 years from a CF patient. Chemical structure by MS spectrometry defined lipopolysaccharide (LPS) lipid A and peptidoglycan (PGN) muropeptides with specific structural modifications temporally associated with CF lung ..
  78. ncbi Pseudomonas aeruginosa O-antigen chain length is determined before ligation to lipid A core
    Craig Daniels
    Department of Microbiology, University of Guelph, Guelph, Ontario, Canada N1G 2W1
    Environ Microbiol 4:883-97. 2002
    ..novel observation that polymerization of modal chain length-distributed O-antigen occurred before ligation to the lipid A core...
  79. ncbi Oxidative decarboxylation of UDP-glucuronic acid in extracts of polymyxin-resistant Escherichia coli. Origin of lipid a species modified with 4-amino-4-deoxy-L-arabinose
    Steven D Breazeale
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 277:2886-96. 2002
    Addition of the 4-amino-4-deoxy-l-arabinose (l-Ara4N) moiety to the phosphate groups of lipid A is implicated in bacterial resistance to polymyxin and cationic antimicrobial peptides of the innate immune system...
  80. ncbi Elucidation of the MD-2/TLR4 interface required for signaling by lipid IVa
    Catherine Walsh
    Department of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom
    J Immunol 181:1245-54. 2008
    ....
  81. pmc The PmrA-regulated pmrC gene mediates phosphoethanolamine modification of lipid A and polymyxin resistance in Salmonella enterica
    Hyunwoo Lee
    Department of Molecular Microbiology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Bacteriol 186:4124-33. 2004
    The PmrA/PmrB regulatory system of Salmonella enterica controls the modification of lipid A with aminoarabinose and phosphoethanolamine...
  82. pmc PmrAB, a two-component regulatory system of Pseudomonas aeruginosa that modulates resistance to cationic antimicrobial peptides and addition of aminoarabinose to lipid A
    Samuel M Moskowitz
    Department of Pediatrics, University of Washington School of Medicine, Seattle, Washington 98195, USA
    J Bacteriol 186:575-9. 2004
    ..b>Lipid A of these mutants contained aminoarabinose, an inducible modification that is associated with polymyxin resistance...
  83. pmc Altered linkage of hydroxyacyl chains in lipid A of Campylobacter jejuni reduces TLR4 activation and antimicrobial resistance
    Andries van Mourik
    Department of Infectious Diseases and Immunology, Utrecht University, Yalelaan 1, 3584 CL Utrecht, The Netherlands
    J Biol Chem 285:15828-36. 2010
    Modification of the lipid A moiety of bacterial lipopolysaccharide influences cell wall properties, endotoxic activity, and bacterial resistance to antimicrobial peptides...
  84. pmc Identification of a second lipopolysaccharide in Porphyromonas gingivalis W50
    Minnie Rangarajan
    Centre for Infectious Disease, Institute of Cell and Molecular Science, Barts and The London Queen Mary s School of Medicine and Dentistry, 4 Newark Street, London E1 2AT, United Kingdom
    J Bacteriol 190:2920-32. 2008
    ..APS confirmed the previous structure but also revealed additional signals that suggested the presence of a lipid A. This was confirmed by fatty acid analysis of the APS and matrix-assisted laser desorption ionization-time of ..
  85. ncbi Lipid A antagonist, lipid IVa, is distinct from lipid A in interaction with Toll-like receptor 4 (TLR4)-MD-2 and ligand-induced TLR4 oligomerization
    Shin Ichiroh Saitoh
    Division of Infectious Genetics, Institute of Medical Science, University of Tokyo, Tokyo, Japan
    Int Immunol 16:961-9. 2004
    Toll-like receptor 4 (TLR4) and MD-2 recognizes lipid A, the active moiety of microbial lipopolysaccharide (LPS). Little is known about mechanisms for LPS recognition by TLR4-MD-2...
  86. ncbi Protective efficacy of a tandemly linked, multi-subunit recombinant leishmanial vaccine (Leish-111f) formulated in MPL adjuvant
    Yasir A W Skeiky
    Corixa Corporation, 1124 Columbia Street, Suite 200, Seattle, WA 98104, USA
    Vaccine 20:3292-303. 2002
    ..We report that monophosphoryl lipid A (MPL) plus squalene (MPL-SE) formulated with rLeish-111f elicited protective immunity against L. major infection...
  87. ncbi Enhanced humoral and Type 1 cellular immune responses with Fluzone adjuvanted with a synthetic TLR4 agonist formulated in an emulsion
    Susan L Baldwin
    Infectious Disease Research Institute, 1124 Columbia Street, Suite 400, Seattle, WA 98104, United States
    Vaccine 27:5956-63. 2009
    ..In this study, the activity of three adjuvants, an oil-in-water emulsion and a synthetic lipid A adjuvant formulated with or without the emulsion, is compared...
  88. pmc Novel modification of lipid A of Francisella tularensis
    Nancy J Phillips
    Department of Pharmaceutical Chemistry, University of California, San Francisco, California, USA
    Infect Immun 72:5340-8. 2004
    We have investigated the lipid A of Francisella tularensis subsp...
  89. ncbi Function of the Escherichia coli msbB gene, a multicopy suppressor of htrB knockouts, in the acylation of lipid A. Acylation by MsbB follows laurate incorporation by HtrB
    T Clementz
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 272:10353-60. 1997
    ..htrB encodes the lauroyl transferase of lipid A biosynthesis that acylates the intermediate (Kdo)2-lipid IVA (Brozek, K. A., and Raetz, C. R. H. (1990) J. Biol...
  90. ncbi WaaL of Pseudomonas aeruginosa utilizes ATP in in vitro ligation of O antigen onto lipid A-core
    Priyanka D Abeyrathne
    Department of Molecular and Cellular Biology, University of Guelph, Guelph, ON, N1G 2W1, Canada
    Mol Microbiol 65:1345-59. 2007
    ..The substrates for the O-antigen ligase assay, O-antigen-Und-P and lipid A-core were prepared from a waaL mutant...
  91. ncbi Lipid A modifications in polymyxin-resistant Salmonella typhimurium: PMRA-dependent 4-amino-4-deoxy-L-arabinose, and phosphoethanolamine incorporation
    Z Zhou
    Department of Biochemistry and the Duke NMR Spectroscopy Center, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 276:43111-21. 2001
    b>Lipid A of Salmonella typhimurium can be resolved into multiple molecular species. Many of these substances are more polar than the predominant hexa-acylated lipid A 1,4'-bisphosphate of Escherichia coli K-12...
  92. ncbi A PhoP/PhoQ-induced Lipase (PagL) that catalyzes 3-O-deacylation of lipid A precursors in membranes of Salmonella typhimurium
    M S Trent
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 276:9083-92. 2001
    Pathogenic bacteria modify the structure of the lipid A portion of their lipopolysaccharide in response to environmental changes. Some lipid A modifications are important for virulence and resistance to cationic antimicrobial peptides...
  93. ncbi An inner membrane enzyme in Salmonella and Escherichia coli that transfers 4-amino-4-deoxy-L-arabinose to lipid A: induction on polymyxin-resistant mutants and role of a novel lipid-linked donor
    M S Trent
    Department of Biochemistry, Duke NMR Spectroscopy Center, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 276:43122-31. 2001
    Attachment of the cationic sugar 4-amino-4-deoxy-l-arabinose (l-Ara4N) to lipid A is required for the maintenance of polymyxin resistance in Escherichia coli and Salmonella typhimurium...
  94. pmc Immunization with a polyprotein vaccine consisting of the T-Cell antigens thiol-specific antioxidant, Leishmania major stress-inducible protein 1, and Leishmania elongation initiation factor protects against leishmaniasis
    Rhea N Coler
    Infectious Disease Research Institute, Seattle, Washington 98104, USA
    Infect Immun 70:4215-25. 2002
    ....
  95. ncbi Role for MyD88-independent, TRIF pathway in lipid A/TLR4-induced endotoxin tolerance
    Subhra K Biswas
    Singapore Immunology Network, Biomedical Sciences Institutes, Agency for Science, Technology and Research, Immunos
    J Immunol 179:4083-92. 2007
    ..We investigated the role of the TRIF/IFN-beta pathway in TLR4-induced endotoxin tolerance. Lipid A-induced homotolerance was characterized by the down-regulation of MyD88-dependent proinflammatory cytokines TNF-..
  96. ncbi Lipid A modifications characteristic of Salmonella typhimurium are induced by NH4VO3 in Escherichia coli K12. Detection of 4-amino-4-deoxy-L-arabinose, phosphoethanolamine and palmitate
    Z Zhou
    Department of Biochemistry, Duke University Medical Center, Box 3711, Durham, North Carolina 27710, USA
    J Biol Chem 274:18503-14. 1999
    Two-thirds of the lipid A in wild-type Escherichia coli K12 is a hexa-acylated disaccharide of glucosamine in which monophosphate groups are attached at positions 1 and 4'...
  97. ncbi Efficacy and tolerability of short-term specific immunotherapy with pollen allergoids adjuvanted by monophosphoryl lipid A (MPL) for children and adolescents
    K J Drachenberg
    Bencard Allergie GmbH, Munich, Germany
    Allergol Immunopathol (Madr) 31:270-7. 2003
    ..immunotherapy (SIT) with pollen allergoids formulated with the Th1-inducing adjuvant 3-deacylated monophosphoryl lipid A (MPL adjuvant, Corixa) has shown good efficacy and tolerability in the treatment of pollen allergies in adults...
  98. pmc Altered lipid A structures and polymyxin hypersensitivity of Rhizobium etli mutants lacking the LpxE and LpxF phosphatases
    Brian O Ingram
    Department of Biochemistry, Duke University Medical Center, Durham, NC 27710, USA
    Biochim Biophys Acta 1801:593-604. 2010
    The lipid A of Rhizobium etli, a nitrogen-fixing plant endosymbiont, displays significant structural differences when compared to that of Escherichia coli. An especially striking feature of R...
  99. ncbi A derivative of lipid A is involved in signal recognition particle/SecYEG-dependent and -independent membrane integrations
    Ken ichi Nishiyama
    Institute of Biochemistry and Molecular Biology, Centre of Biochemistry and Molecular Cell Research, University of Freiburg, Hermann Herder Strasse 7, D 79104 Freiburg, Germany
    J Biol Chem 281:35667-76. 2006
    ..This factor was found to be a lipid A-derived membrane component possessing a peptide moiety.
  100. pmc The Toll-like receptor 4 agonist monophosphoryl lipid a augments innate host resistance to systemic bacterial infection
    Christopher D Romero
    Department of Anesthesiology, University of Texas Medical Branch, Galveston, TX 77555 0591, USA
    Infect Immun 79:3576-87. 2011
    Monophosphoryl lipid A (MPLA) is a Toll-like receptor 4 (TLR4) agonist that is currently used as a vaccine adjuvant in humans...
  101. pmc The lipid A phosphate position determines differential host Toll-like receptor 4 responses to phylogenetically related symbiotic and pathogenic bacteria
    Stephen R Coats
    Department of Periodontics, School of Dentistry, University of Washington, 1959 NE Pacific St, HSB, Box 357444, Seattle, WA 98195, USA
    Infect Immun 79:203-10. 2011
    ..gingivalis synthesize lipopolysaccharides (LPS) consisting of penta-acylated, monophosphorylated lipid A in addition to immunologically silent, nonphosphorylated lipid A, they elicit strikingly distinct Toll-like ..

Research Grants63

  1. Targeting superbugs: discovery and development of new broad-spectrum lipopeptides
    Jian Li; Fiscal Year: 2013
    ..Our approach, based upon modeling the interaction between polymyxins and the lipid A of lipopolysaccharides (LPS), is novel...
  2. Mechanisms of adaptive immunity to P. aeruginosa in the lung
    Gregory P Priebe; Fiscal Year: 2013
    ..Finally, we will assess whether expression of heterologous O antigens by the vaccine or changes in its LPS lipid A acylation pattern can enhance its effectiveness...
  3. LIPID A MODIFICATION SYSTEMS IN GRAM-NEGATIVE BACTERIA
    Pei Zhou; Fiscal Year: 2012
    DESCRIPTION (provided by applicant): The lipid A moiety of lipopolysaccharide (LPS) forms the outer monolayer of the outer membrane of most Gram-negative bacteria...
  4. Lipid A &Innate Immune Receptors in Neisseria Infection
    Gary A Jarvis; Fiscal Year: 2013
    ..Our work and that of others has shown that the lipid A (LA) portion of Neisserial LOS engages innate immune receptor toll-like receptor 4 (TLR4) to initiate a signaling ..
  5. Gonococcal Mechanisms to Evade Host Defenses
    WILLIAM MAURICE SHAFER; Fiscal Year: 2013
    ..normal human serum (NHS) is genetically determined through structural alterations in the core oligosaccharide and lipid A components of the gonococcal LOS...
  6. BIOSYNTHESIS AND FUNCTION OF LIPOPOLYSACCHARIDES
    Pei Zhou; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): The lipid A moiety of lipopolysaccharide (LPS) forms the outer monolayer of the outer membrane of most Gram-negative bacteria...
  7. Spin labeling of MsbA
    Candice S Klug; Fiscal Year: 2012
    ..Specifically, MsbA is the ABC transporter for lipid A that is found in the inner membranes of Gram-negative bacteria such as Escherichia coli, Salmonella typhimurium, ..
  8. Augmentation of Innate Anti-Microbial Immunity by TLR4 Agonists
    Edward R Sherwood; Fiscal Year: 2013
    ..Our studies show that treatment with the toll-like receptor 4 (TLR4) agonist monophosphoryl lipid A (MPLA) is effective in improving innate host resistance to Pseudomonas aeruginosa burn wound sepsis in mice...
  9. Structural and Biochemical Studies of LpxC Inhibition
    Pei Zhou; Fiscal Year: 2012
    Project Summary/Abstract Lipid A (endotoxin) is a glucosamine-based saccharolipid that constitutes the outer monolayer of the outer membrane of Gram-negative bacteria;it is also the active component of lipopolysaccharide that causes life-..
  10. Gram-Negative Pneumonia and Lipopolysaccharide Binding Protein
    MARK RICHARD HEMMILA; Fiscal Year: 2010
    ..LBP is an acute phase protein that recognizes the lipid A moiety of LPS...
  11. Immunotherapeutic Potential of Modified Lipooligosaccharides and Lipid A's
    Robert K Ernst; Fiscal Year: 2013
    ..Recently, the lipid A mimetic (monophosphoryl lipid A, MPL) adjuvant has been combined with alum (AS04) in two FDA-approved vaccines (..
  12. PHOP REGULON AND SALMONELLA VIRULENCE
    Samuel I Miller; Fiscal Year: 2013
    ..surfaces and within phagocytic cell granules and cytokines produced in response to recognition of bacterial lipid A. Pathogens such as Salmonellae have mechanisms to resist these killing mechanisms that are environmentally ..
  13. Laser-based powder vaccine delivery for improved newborn immunization
    Xinyuan Chen; Fiscal Year: 2013
    ..A laser-based powder delivery (LPD) in combination with a clinical monophosphoryl lipid A (MPL) adjuvant (MPL/LPD) is proposed for improved newborn immunization...
  14. Pandemic H5N1 vaccine containing recombinant H5 and a synthetic TLR4 agonist, GLA
    Christopher H Clegg; Fiscal Year: 2010
    ..proof of concept experiments where rH5 will be formulated with an oil-in-water emulsion and Glucopyranosyl Lipid A (GLA), a synthetic Toll-Like Receptor-4 (TLR-4) agonist...
  15. Pseudomonas aeruginosa lipid A
    Robert K Ernst; Fiscal Year: 2010
    ..by an inflammatory process that results, at least in part, from stimulation of the innate immune system by PA lipid A, the bioactive component of lipopolysaccharide (IPS)...
  16. The Role of TLR4 and RSV F Protein in Immunity to RSV
    JORGE C BLANCO; Fiscal Year: 2013
    ..FI-RSV used in the failed trials, newly formulated with a non-toxic adjuvant and TLR4 agonist, monophosphoryl lipid A (MPL), suppressed FI-RSV vaccine-enhanced disease by blunting the mixed Th1- and Th2-type "cytokine storm" that ..
  17. Mass Spectrometric Characterization of Lipopolysaccharides
    Jennifer S Brodbelt; Fiscal Year: 2013
    ..spectrometric approaches for characterization of the complex lipopolysaccharides (LPS), including the endotoxic lipid A sub-unit, that comprise the key constituents of the outer membrane of Gram-negative bacteria...
  18. Immunizing Against Malaria by Inducing Both Protective Antibodies and CD8 T Cells
    B Kim Lee Sim; Fiscal Year: 2013
    ..It is administered with an adjuvant AS01, which includes liposomes, monophosphoryl lipid A, and a purified plant extract, QS21, but was initially developed with an oil in water-based adjuvant...
  19. Metabolic Engineering of Cancer for Immunotargeting
    Zhongwu Guo; Fiscal Year: 2012
    ..are: 1) to synthesize and study new conjugate vaccines with the unnatural TACA analogs linked to monophosphoryl lipid A and a peptidic T cell epitope;2) to develop a method to quantitatively analyze the expression of unnatural TACA ..
  20. Discovery of Polymyxin-based Antibacterial Agents Active Against Multi-Drug Resis
    Lawrence H Lash; Fiscal Year: 2013
    ..They will also be profiled for binding to the bacterial membranes and molecular target (Lipid A)...
  21. Novel vaccine strategies for prevention of N. meningitidis group B disease
    Dan M Granoff; Fiscal Year: 2013
    ..remove endotoxin from conventional OMV vaccines extract fHbp, we attenuate endotoxin activity by inactivating a lipid A biosynthesis gene, LpxL1...
  22. Mechanisms of Resistance in Gram-Negative Bacteria
    Marcelo Carlos Sousa; Fiscal Year: 2010
    ..Pseudomonas isolated from Cystic Fibrosis patients have specific, virulence-associated modifications in their lipid A structure...
  23. Alteration of lipid A acyl chain length in Salmonella
    Qingke Kong; Fiscal Year: 2013
    ..Many of these symptoms are consistent with known reactions to lipid A. Lipid A interacts with the human immune system via the toll-like receptor 4 (TLR4) which recognizes specific ..
  24. Development of a Rationally Attenuated Live Vaccine for Francisella tularensis
    Stefanie N Vogel; Fiscal Year: 2013
    ..We now show that a similar mutation in Ft LVS resulted in the same structural modification to the lipid A and was avirulent at >106 LD50 after subcutaneous infection of C57BL/6 and BALB/c mice...
  25. Neisserial Porins and Antigen Presenting Cells
    LEE MARK WETZLER; Fiscal Year: 2013
    ..Alum (inflammasomes mediated immune activation, other TLR ligands, including CpG DNA (TLR9), and monophosphoryl lipid A (MPL)(TLR4), and QS-21...
  26. Bacterial Surface Structures of Helicobacter Pylori and Campylobacter Jejuni
    MICHAEL STEPHEN TRENT; Fiscal Year: 2013
    ..LPS is anchored to the bacterial cell by its lipid anchor known as lipid A. Lipid A is synthesized via a highly conserved pathway at the cytoplasmic face of the inner membrane...
  27. The role of LPS-TLR4 signaling in live vaccine-induced protective responses
    Egil Lien; Fiscal Year: 2013
    ..TLR4 is the cellular receptor for LPS via its lipid A. We generated a new Y. pestis strain expressing LpxL, an E...
  28. Mechanisms of Monophosporyl Lipid A Immuno-Modulation in Septic Shock
    CHRISTOPHER DAVID MICHAEL ROMERO; Fiscal Year: 2010
    ..Monophosphoryl Lipid A (MPLA) is an endotoxin derivative used as a vaccine adjuvant...
  29. Molecular Determinants of Endotoxin Interaction with Toll-like Receptor4
    Theresa Lee Gioannini; Fiscal Year: 2013
    ..T399I in the TLR4 ectodomain on surface expression and function of TLR4;and 3) the effects of variables in E (lipid A) structure and presentation on induction of MyD88- vs. TRIF-dependent signaling by activated TLR4...
  30. Therapeutic Synergy of Membrane-Anchored Cytokines, TLR Ligands &Ukrain
    Erica Bozeman; Fiscal Year: 2012
    ..immune cells of the adaptive immune response, the simultaneous vaccination with the TLR- ligands, monophosphoryl lipid A (MPL) and unmethylated CpG-motifs (CpG), will activate innate immune cells, most notably DCs that will further ..
  31. The Outer Surface of Vibrio cholerae
    MICHAEL STEPHEN TRENT; Fiscal Year: 2012
    ..cholerae is composed of three distinct regions the membrane associated lipid A domain, a short core oligosaccharide, and the O-antigen polysaccharide...
  32. LpxC inhibitors as a novel class of antibiotics against N. gonorrhoeae
    Pei Zhou; Fiscal Year: 2013
    ..The goal of this proposal is to optimize inhibitors of LpxC, an essential enzyme in the lipid A biosynthetic pathway, for treatment of N. gonorrhoeae infections...
  33. Preclinical development of DS-96, a novel alkylpolyamine endotoxin squestrant
    SUNIL ABRAHAM DAVID; Fiscal Year: 2012
    ..simple and synthetically easily accessible molecules of the lipopolyamine class specifically bind to the toxic "Lipid A" moiety of LPS and neutralize its toxicity...
  34. The Outer Surface of Vibrio cholerae
    MICHAEL STEPHEN TRENT; Fiscal Year: 2013
    ..the outer membrane is a unique, asymmetric bilayer with glycerophospholipids confined to the inner leaflet and lipid A, a unique saccharolipid, localized to the outer leaflet...
  35. Toll like receptors in bacterial keratitis
    Eric Pearlman; Fiscal Year: 2012
    ..aeruginosa and S. marcescens Lipid A composition with TLR4/MD-2 reactivity In addition to increasing our understanding of how the corneal epithelium ..
  36. ArmR: a novel drug target and mediator of antibiotic resistance
    David S Weiss; Fiscal Year: 2013
    ..even to the "last line of defense" drugs, polymyxin B and colistin (polymyxin E), which target and disrupt the lipid A portion of lipopolysaccharide (LPS) in the outer membrane...
  37. Delivery and Adjuvantation of Nicotine Vaccine by Laser Illumination
    Xinyuan Chen; Fiscal Year: 2013
    ..Encapsulation of nicotine vaccine and a safe cutaneous monophosphoryl lipid A (MPL) adjuvant into mixed poly(D,L-lactic-co-glycolic acid) (PLGA) particles with different sizes is expected to ..
  38. Innate immune response to microbial PAMPs in the schistosome-transmitting snail,
    John T Sullivan; Fiscal Year: 2012
    ..e., lipid A or the O polysaccharide) will be identified...
  39. Rapid Analytics for Endotoxin using Liquid Crystalline Droplets
    Nicholas L Abbott; Fiscal Year: 2012
    ..optimization of the analytic method: Specific hypotheses are formulated to test the role of the structure of lipid A on the ordering of LCs...
  40. L. Brazilensis Vaccine Antigens and T-cell Quality in Protection
    Lynn Soong; Fiscal Year: 2013
    ..tested via DNA- and protein-based immunization regimens, in conjunction with novel TLR4- adjuvants glucopyranosyl lipid A (GLA) and monophosphoryl lipid A (MPL)...
  41. RBD recombinant protein-based SARS vaccine for biodefense
    Shibo Jiang; Fiscal Year: 2013
    ..The specific product quality assays and vaccine formulations with alum and/or glucopyrranosyl lipid A (GLA), an innate adjuvant, will be developed...
  42. Regulation of MD-2 function and expression
    Jerrold P Weiss; Fiscal Year: 2013
    ..g., metabolically labeled native and synthetic E and lipid A variants, recombinant wild-type and mutant human E-binding proteins and TLR4 ectodomain, monoclonal antibodies, ..
  43. PHAGOCYTE RECEPTORS FOR LIPID A
    Douglas T Golenbock; Fiscal Year: 2013
    ..g., MyD88, TRIP, Unc93b, ASC, etc) with a strain of Y pestis in which the acylation pattern of lipid A, as well as the bioactivity, is genetically controlled...
  44. The Role of LPS and Toll-like Receptors in Plague
    Egil Lien; Fiscal Year: 2010
    ..Y. pestis and some other pathogens have the ability to modify the acyl chains in their lipopolysaccharide (LPS) /lipid A in order to minimize Toll-like receptor 4 (TLR4) signaling. Consequently, Y...
  45. REGULATION OF THICK ASCENDING LIMB ACID-BASE TRANSPORT
    DAVID WILLIAM GOOD; Fiscal Year: 2013
    ..Monophosphoryl lipid A (MPLA) is a detoxified derivative of LPS that retains the parent compound's beneficial immunomodulatory ..
  46. The human B cell toll-like receptor 4 complex
    Lisa M Ganley-Leal; Fiscal Year: 2013
    ..coli LPS. In contrast, TLR4+ B cells respond to LPS molecules with characteristics of hypo-acylated lipid A, a group of ligands shown to be antagonistic for myeloid TLR4...
  47. Genetics and biosynthesis of an O antigen essential for symbiosis
    KENNETH D NOEL; Fiscal Year: 2010
    ..the structure of the entire LPS is almost completely solved, most of the steps in the synthesis of the lipid A and core portion of the molecule have been demonstrated in vitro, and a 30 kb cluster of genes that specify most ..
  48. Innate and Adaptive Immunity in Experimental and Human Gonoccocal Infection
    Peter A Rice; Fiscal Year: 2013
    ..gonorrhoeae) biology to understand the binding of LOS derived lipid A with its direct ligand that serves as an intermediary structure to activate and permit signaling of toll-like ..
  49. XV INTERNATIONAL CONGRESS OF NUTRITION
    RICHARD ALLISON; Fiscal Year: 1993
    ..LBP forms a high affinity complex with the lipid A portion of LPS and together this complex binds to the monocytic differentiation antigen CD14 to upregulated tumor ..
  50. P Gingivalis LPS: Hemin-induced lipid A structural remodelling
    RICHARD PETERS DARVEAU; Fiscal Year: 2013
    ..P. gingivalis lipopolysaccharide (LPS) displays an unusual amount of lipid A structural heterogeneity which we hypothesized may be a potential modulator of the innate host defense response...
  51. Markers predicting response to therapy for KPC-producing Klebsiella pneumoniae
    Yohei Doi; Fiscal Year: 2013
    ..will correlate colistin and doripenem MICs with the presence of key resistance mechanisms against these agents (lipid A modifications for colistin, and the expression levels of blaKPC and ompK35/36 encoding major porins for doripenem)..
  52. Research and Development of a Novel System to Produce Polysaccharide Conjugate Va
    Peng Wang; Fiscal Year: 2009
    ..Two genes (wecA: initial glycosyltransfer reaction, waaL: ligation of nascent polysaccharide chains to the core-Lipid A) which are vital to the LPS biosynthetic pathway and may interfere with PglL O-glycosylation will be disrupted...
  53. ApoVax104-HPV as a Novel Vaccine for Cervical Cancer
    KATHRYN MACLEOD; Fiscal Year: 2009
    ..E7 oncogene (E749-57) was more effective than 3 benchmark adjuvants (lipopolysaccharide, (LPS), Monophosphoryl Lipid A (MPL), and CpG oligonucleotide (CpG), in the generation of primary and long- term T cell memory as well as in the ..
  54. A nanoparticle-based vaccine against leishmaniasis
    DIANE MCMAHON PRATT; Fiscal Year: 2012
    ..into PLGA nanoparticles containing one of two adjuvants, namely a CpG oligonucleotide and/or monophosphoryl lipid A (MPLA)...
  55. REGULATION OF IMMUNE RESPONSE IN THE ORAL CAVITY
    Suzanne Michalek; Fiscal Year: 2003
    ..The adjuvants to be used are the B subunit of cholera toxin (rCTB) and monophosphoryl lipid A (MPL). Adult volunteers will be used in this aspect of the study...
  56. Adjuvant Functions of Detoxified LPS
    Thomas C Mitchell; Fiscal Year: 2012
    DESCRIPTION (provided by applicant): Monophosphoryl lipid A (MLA) is a detoxified form of TLR4 agonist LPS that is approved for use as a vaccine adjuvant in Europe and is nearing approval for use in the US...
  57. Modification of Helicobacter pylori Lipid A
    MICHAEL TRENT; Fiscal Year: 2004
    The outer membrane of Gram-negative bacteria consists of a unique molecule known as lipid A that serves as the membrane anchor for lipopolysaccharide (LPS)...
  58. Endotoxin Neutralization by HDL-Mimetic Peptide
    Himanshu Gupta; Fiscal Year: 2010
    ..One mechanism by which HDL neutralizes LPS is thought to occur by insertion and masking of the lipid A domain of LPS into the phospholipid leaflet that covers the surface of HDL...
  59. Adjuvant Development
    David Johnson; Fiscal Year: 2013
    ..of host defense systems via their interaction with TLR4, but the toxicity of LPS and its active principle, lipid A, have precluded their use as adjuvants...
  60. DEVELOP AND EVALUATE NEW LEPROSY AND TB VACCINES
    Thomas Gillis; Fiscal Year: 2003
    ..of BCG, 2) leucine auxotroph of MT, 3) MT culture filtrate in adjuvant prepared from the nontoxic derivative of lipid A from Salmonella minnesota (MPL, [plus IL-2]) and 4) pooled MT genomic vaccine, (3) test protective efficacy, ..
  61. LIPOOLIGOSACCHARIDES OF HAEMOPHILUS INFLUENZAE
    Michael Apicella; Fiscal Year: 2003
    The lipooligosaccharides of Haemophilus influenzae are important virulence factors. The lipid A portion of the lipooligosaccharide (LOS) is responsible in part for the toxicity associated with this organism...
  62. STRUCTURAL ANALYSIS OF LIPOPOLYSACCHARIDES AND LIPID A
    Kuni Takayama; Fiscal Year: 1993
    ..of B lymphocytes form nonresponder C3H/Hej mice within the structural series of precursor IVA, monophosphoryl lipid A, diphosphoryl lipid A, ReLPS and RdLPS...
  63. Structure, mechanism and evolution of KDO8P synthase
    DOMENICO GATTI; Fiscal Year: 2007
    ..This eight carbon sugar is the first component of the oligosaccharide core region that links the lipid A moiety of LPS to the O-antigen...