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Burkholderia mallei expresses a unique lipopolysaccharide mixture that is a potent activator of human Toll‐like receptor 4 complexes
Author(s) -
Brett Paul J.,
Burtnick Mary N.,
Snyder D. Scott,
Shan Jeffrey G.,
Azadi Parastoo,
Gherardini Frank C.
Publication year - 2007
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/j.1365-2958.2006.05519.x
Subject(s) - lipid a , biology , lipopolysaccharide , microbiology and biotechnology , toll like receptor , biochemistry , receptor , amino acid , innate immune system , immunology
Summary 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‐α, 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.