title: Burkholderia mallei expresses a unique lipopolysaccharide mixture that is a potent activator of human Toll-like receptor 4 complexes.
abstract: Burkholderia mallei, the aetiologic agent of glanders, causes a variety of illnesses in animals and humans ranging from occult infections to acute fulminating septicaemias. To better understand the role of lipopolysaccharide (LPS) in the pathogenesis of these diseases, studies were initiated to characterize the structural and biological properties of lipid A moieties expressed by this organism. Using a combination of chemical analyses and MALDI-TOF mass spectrometry, B. mallei was shown to express a heterogeneous mixture of tetra- and penta-acylated lipid A species that were non-stoichiometrically substituted with 4-amino-4-deoxy-arabinose residues. The major penta-acylated species consisted of bisphosphorylated d-glucosamine disaccharide backbones possessing two amide linked 3-hydroxyhexadecanoic acids, two ester linked 3-hydroxytetradecanoic acids [C14:0(3-OH)] and an acyloxyacyl linked tetradecanoic acid, whereas, the major tetra-acylated species possessed all but the 3'-linked C14:0(3-OH) residues. In addition, although devoid of hexa-acylated species, B. mallei LPS was shown to be a potent activator of human Toll-like receptor 4 complexes and stimulated human macrophage-like cells (THP-1 and U-937), monocyte-derived macrophages and dendritic cells to produce high levels of TNF-alpha, IL-6 and RANTES. Based upon these results, it appears that B. mallei LPS is likely to play a significant role in the pathogenesis of human disease.
authors.affiliation: Laboratory of Zoonotic Pathogens, Rocky Mountain Laboratories, NIAID, NIH, Hamilton, MT 59840, USA.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Brett
authors.forename: Mary N
authors.initials: MN
authors.lastname: Burtnick
authors.forename: D Scott
authors.initials: DS
authors.lastname: Snyder
authors.forename: Jeffrey G
authors.initials: JG
authors.lastname: Shannon
authors.forename: Parastoo
authors.initials: P
authors.lastname: Azadi
authors.forename: Frank C
authors.initials: FC
authors.lastname: Gherardini
mesh_terms: D042726:Burkholderia mallei / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D018946:Chemokine CCL5 / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology / Q000382:microbiology; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000096:biosynthesis / Q000737:chemistry / Q000276:immunology*; D008264:Macrophages / Q000276:immunology / Q000382:microbiology; D013058:Mass Spectrometry; D009000:Monocytes / Q000276:immunology / Q000382:microbiology; D051197:Toll-Like Receptor 4 / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D018946:Chemokine CCL5; D015850:Interleukin-6; D008070:Lipopolysaccharides; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha