Comprehensive analysis of clinical Burkholderia pseudomallei isolates demonstrates conservation of unique lipid A structure and TLR4-dependent innate immune activation.
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 hig...
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ftdoajarticles:oai:doaj.org/article:ff5e59f8bb49400ebc92ad40efaf31f7 2023-05-15T15:15:40+02:00 Comprehensive analysis of clinical Burkholderia pseudomallei isolates demonstrates conservation of unique lipid A structure and TLR4-dependent innate immune activation. Sineenart Sengyee Sung Hwan Yoon Suporn Paksanont Thatcha Yimthin Vanaporn Wuthiekanun Direk Limmathurotsakul T Eoin West Robert K Ernst Narisara Chantratita 2018-02-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0006287 https://doaj.org/article/ff5e59f8bb49400ebc92ad40efaf31f7 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC5842036?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0006287 https://doaj.org/article/ff5e59f8bb49400ebc92ad40efaf31f7 PLoS Neglected Tropical Diseases, Vol 12, Iss 2, p e0006287 (2018) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2018 ftdoajarticles https://doi.org/10.1371/journal.pntd.0006287 2022-12-30T23:21:17Z 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. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 12 2 e0006287 |
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Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
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English |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Sineenart Sengyee Sung Hwan Yoon Suporn Paksanont Thatcha Yimthin Vanaporn Wuthiekanun Direk Limmathurotsakul T Eoin West Robert K Ernst Narisara Chantratita Comprehensive analysis of clinical Burkholderia pseudomallei isolates demonstrates conservation of unique lipid A structure and TLR4-dependent innate immune activation. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
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. |
format |
Article in Journal/Newspaper |
author |
Sineenart Sengyee Sung Hwan Yoon Suporn Paksanont Thatcha Yimthin Vanaporn Wuthiekanun Direk Limmathurotsakul T Eoin West Robert K Ernst Narisara Chantratita |
author_facet |
Sineenart Sengyee Sung Hwan Yoon Suporn Paksanont Thatcha Yimthin Vanaporn Wuthiekanun Direk Limmathurotsakul T Eoin West Robert K Ernst Narisara Chantratita |
author_sort |
Sineenart Sengyee |
title |
Comprehensive analysis of clinical Burkholderia pseudomallei isolates demonstrates conservation of unique lipid A structure and TLR4-dependent innate immune activation. |
title_short |
Comprehensive analysis of clinical Burkholderia pseudomallei isolates demonstrates conservation of unique lipid A structure and TLR4-dependent innate immune activation. |
title_full |
Comprehensive analysis of clinical Burkholderia pseudomallei isolates demonstrates conservation of unique lipid A structure and TLR4-dependent innate immune activation. |
title_fullStr |
Comprehensive analysis of clinical Burkholderia pseudomallei isolates demonstrates conservation of unique lipid A structure and TLR4-dependent innate immune activation. |
title_full_unstemmed |
Comprehensive analysis of clinical Burkholderia pseudomallei isolates demonstrates conservation of unique lipid A structure and TLR4-dependent innate immune activation. |
title_sort |
comprehensive analysis of clinical burkholderia pseudomallei isolates demonstrates conservation of unique lipid a structure and tlr4-dependent innate immune activation. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2018 |
url |
https://doi.org/10.1371/journal.pntd.0006287 https://doaj.org/article/ff5e59f8bb49400ebc92ad40efaf31f7 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 12, Iss 2, p e0006287 (2018) |
op_relation |
http://europepmc.org/articles/PMC5842036?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0006287 https://doaj.org/article/ff5e59f8bb49400ebc92ad40efaf31f7 |
op_doi |
https://doi.org/10.1371/journal.pntd.0006287 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
12 |
container_issue |
2 |
container_start_page |
e0006287 |
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1766346022252969984 |