ArticlePLoS neglected tropical diseases2018
Comprehensive analysis of clinical Burkholderia pseudomallei isolates demonstrates conservation of unique lipid A structure and TLR4-dependent innate immune activation.
Article in PLoS neglected tropical diseases, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 20 citations in OpenAlex.
- Pooled it
- Development of an antigen detection test kit (Melioidosis-ATK) for point-of-care diagnosis of melioidosis.Microbiology spectrum · 2026Article
- Targeting inflammasome, IL-1β, and coagulation in melioidosis.Frontiers in microbiology · 2026Review
- An outer membrane vesicle vaccine prevents lung pathology in a macaque model of pneumonic melioidosis.Nature communications · 2025Article
- Dysfunctional host cellular immune responses are associated with mortality in melioidosis.Emerging microbes & infections · 2024Article
- A pH-sensitive motif in an outer membrane protein activates bacterial membrane vesicle production.Nature communications · 2024Article
- Pathogenicity and virulence ofVirulence · 2022Review
- Blood transcriptomics to characterize key biological pathways and identify biomarkers for predicting mortality in melioidosis.Emerging microbes & infections · 2021Article
- Loss of RND-Type Multidrug Efflux Pumps Triggers Iron Starvation and Lipid A Modifications in Pseudomonas aeruginosa.Antimicrobial agents and chemotherapy · 2021Article
- Variation, Modification and Engineering of Lipid A in Endotoxin of Gram-Negative Bacteria.International journal of molecular sciences · 2021Review
- Activation of Toll-Like Receptors by Live Gram-Negative Bacterial Pathogens Reveals Mitigation of TLR4 Responses and Activation of TLR5 by Flagella.Frontiers in cellular and infection microbiology · 2021Article
- Lactoferrin is a dynamic protein in human melioidosis and is a TLR4-dependent driver of TNF-α release in Burkholderia thailandensis infection in vitro.PLoS neglected tropical diseases · 2020Article
- Human Melioidosis.Clinical microbiology reviews · 2020Review
- Lipopolysaccharides from DifferentInfection and immunity · 2019Article
- Efflux Pumps of Burkholderia thailandensis Control the Permeability Barrier of the Outer Membrane.Antimicrobial agents and chemotherapy · 2019Article
- Exonic sequencing identifies TLR1 genetic variation associated with mortality in Thais with melioidosis.Emerging microbes & infections · 2019Article
- Lipid A Remodeling Is a Pathoadaptive Mechanism That Impacts Lipopolysaccharide Recognition and Intracellular Survival of Burkholderia pseudomallei.Infection and immunity · 2018Article
- Engineering xylose metabolism for production of polyhydroxybutyrate in the non-model bacterium Burkholderia sacchari.Microbial cell factories · 2018Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
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-κB 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-κB 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.
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