Taxonomic group: bacteria / Proteobacteria
(Phylum: Proteobacteria)
Host organism: Homo sapiens
Associated disease: melioidosis [ICD11:
1C42 
, ICD11:
XN3LD ];
infection due to Burkholderia pseudomallei [ICD11:
XN3LD ]
The structure was elucidated in this paperNCBI PubMed ID: 29474381Publication DOI: 10.1371/journal.pntd.0006287Journal NLM ID: 101291488Publisher: San Francisco, CA: Public Library of Science
Correspondence: narisara
tropmedres.ac
Institutions: Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand, Department of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand, Department of Microbial Pathogenesis, University of Maryland, Baltimore, MD, United States of America, Department of Tropical Hygiene, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand, Division of Pulmonary and Critical Care Medicine, Harborview Medical Center, University of Washington, Seattle, WA, United States of America, International Respiratory and Severe Illness Center, University of Washington, Seattle, WA, United States of America
Burkholderia pseudomallei is an environmental bacterium that causes melioidosis, a major community-acquired infection in tropical regions. Melioidosis presents with a range of clinical symptoms, is often characterized by a robust inflammatory response, may relapse after treatment, and results in high mortality rates. Lipopolysaccharide (LPS) of B. pseudomallei is a potent immunostimulatory molecule comprised of lipid A, core, and O-polysaccharide (OPS) components. Four B. pseudomallei LPS types have been described based on SDS-PAGE patterns that represent the difference of OPS-type A, type B, type B2 and rough LPS. The majority of B. pseudomallei isolates are type A. We used matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) followed by electrospray ionization quadrupole time-of-flight mass spectrometry (ESI-QqTOF MS) and gas chromatography to characterize the lipid A of B. pseudomallei within LPS type A isolates. We determined that B. pseudomallei lipid A is represented by penta- and tetra-acylated species modified with 4-amino-4-deoxy-arabinose (Ara4N). The MALDI-TOF profiles from 171 clinical B. pseudomallei isolates, including 68 paired primary and relapse isolates and 35 within-host isolates were similar. We did not observe lipid A structural changes when the bacteria were cultured in different growth conditions. Dose-dependent NF-kappa B activation in HEK cells expressing TLR4 was observed using multiple heat-killed B. pseudomallei isolates and corresponding purified LPS. We demonstrated that TLR4-dependent NF-kappa B activation induced by heat-killed bacteria or LPS prepared from OPS deficient mutant was significantly greater than those induced by wild type B. pseudomallei. These findings suggest that the structure of B. pseudomallei lipid A is highly conserved in a wide variety of clinical and environmental circumstances but that the presence of OPS may modulate LPS-driven innate immune responses in melioidosis.
structure, lipid A, Burkholderia pseudomallei, immune response, melioidosis, TLR4
Structure type: oligomer ; 1511
Location inside paper: fig.2, tetraacylated lipid A
Compound class: lipid A
Contained glycoepitopes: IEDB_141807,IEDB_151531
Methods: SDS-PAGE, GC, Western blotting, MALDI-TOF MS, statistical analysis, ESI-QTOF-MS, mutagenesis, microextraction
Related record ID(s): 12783, 12784, 12976
NCBI Taxonomy refs (TaxIDs): 272560
Show glycosyltransferases
There is only one chemically distinct structure:
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