Glyburide reduces bacterial dissemination in a mouse model of melioidosis.
Burkholderia pseudomallei infection (melioidosis) is an important cause of community-acquired Gram-negative sepsis in Northeast Thailand, where it is associated with a ~40% mortality rate despite antimicrobial chemotherapy. We showed in a previous cohort study that patients taking glyburide ( = glib...
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ftdoajarticles:oai:doaj.org/article:2882ae12f52944739cca9b84fe471122 2023-05-15T15:16:14+02:00 Glyburide reduces bacterial dissemination in a mouse model of melioidosis. Gavin C K W Koh Tassili A Weehuizen Katrin Breitbach Kathrin Krause Hanna K de Jong Liesbeth M Kager Arjan J Hoogendijk Antje Bast Sharon J Peacock Tom van der Poll Ivo Steinmetz W Joost Wiersinga 2013-01-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0002500 https://doaj.org/article/2882ae12f52944739cca9b84fe471122 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC3798430?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0002500 https://doaj.org/article/2882ae12f52944739cca9b84fe471122 PLoS Neglected Tropical Diseases, Vol 7, Iss 10, p e2500 (2013) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2013 ftdoajarticles https://doi.org/10.1371/journal.pntd.0002500 2022-12-31T13:35:33Z Burkholderia pseudomallei infection (melioidosis) is an important cause of community-acquired Gram-negative sepsis in Northeast Thailand, where it is associated with a ~40% mortality rate despite antimicrobial chemotherapy. We showed in a previous cohort study that patients taking glyburide ( = glibenclamide) prior to admission have lower mortality and attenuated inflammatory responses compared to patients not taking glyburide. We sought to define the mechanism underlying this observation in a murine model of melioidosis.Mice (C57BL/6) with streptozocin-induced diabetes were inoculated with ~6 × 10(2) cfu B. pseudomallei intranasally, then treated with therapeutic ceftazidime (600 mg/kg intraperitoneally twice daily starting 24 h after inoculation) in order to mimic the clinical scenario. Glyburide (50 mg/kg) or vehicle was started 7 d before inoculation and continued until sacrifice. The minimum inhibitory concentration of glyburide for B. pseudomallei was determined by broth microdilution. We also examined the effect of glyburide on interleukin (IL) 1β by bone-marrow-derived macrophages (BMDM).Diabetic mice had increased susceptibility to melioidosis, with increased bacterial dissemination but no effect was seen of diabetes on inflammation compared to non-diabetic controls. Glyburide treatment did not affect glucose levels but was associated with reduced pulmonary cellular influx, reduced bacterial dissemination to both liver and spleen and reduced IL1β production when compared to untreated controls. Other cytokines were not different in glyburide-treated animals. There was no direct effect of glyburide on B. pseudomallei growth in vitro or in vivo. Glyburide directly reduced the secretion of IL1β by BMDMs in a dose-dependent fashion.Diabetes increases the susceptibility to melioidosis. We further show, for the first time in any model of sepsis, that glyburide acts as an anti-inflammatory agent by reducing IL1β secretion accompanied by diminished cellular influx and reduced bacterial dissemination to distant ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLoS Neglected Tropical Diseases 7 10 e2500 |
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ftdoajarticles |
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English |
topic |
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 Gavin C K W Koh Tassili A Weehuizen Katrin Breitbach Kathrin Krause Hanna K de Jong Liesbeth M Kager Arjan J Hoogendijk Antje Bast Sharon J Peacock Tom van der Poll Ivo Steinmetz W Joost Wiersinga Glyburide reduces bacterial dissemination in a mouse model of melioidosis. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Burkholderia pseudomallei infection (melioidosis) is an important cause of community-acquired Gram-negative sepsis in Northeast Thailand, where it is associated with a ~40% mortality rate despite antimicrobial chemotherapy. We showed in a previous cohort study that patients taking glyburide ( = glibenclamide) prior to admission have lower mortality and attenuated inflammatory responses compared to patients not taking glyburide. We sought to define the mechanism underlying this observation in a murine model of melioidosis.Mice (C57BL/6) with streptozocin-induced diabetes were inoculated with ~6 × 10(2) cfu B. pseudomallei intranasally, then treated with therapeutic ceftazidime (600 mg/kg intraperitoneally twice daily starting 24 h after inoculation) in order to mimic the clinical scenario. Glyburide (50 mg/kg) or vehicle was started 7 d before inoculation and continued until sacrifice. The minimum inhibitory concentration of glyburide for B. pseudomallei was determined by broth microdilution. We also examined the effect of glyburide on interleukin (IL) 1β by bone-marrow-derived macrophages (BMDM).Diabetic mice had increased susceptibility to melioidosis, with increased bacterial dissemination but no effect was seen of diabetes on inflammation compared to non-diabetic controls. Glyburide treatment did not affect glucose levels but was associated with reduced pulmonary cellular influx, reduced bacterial dissemination to both liver and spleen and reduced IL1β production when compared to untreated controls. Other cytokines were not different in glyburide-treated animals. There was no direct effect of glyburide on B. pseudomallei growth in vitro or in vivo. Glyburide directly reduced the secretion of IL1β by BMDMs in a dose-dependent fashion.Diabetes increases the susceptibility to melioidosis. We further show, for the first time in any model of sepsis, that glyburide acts as an anti-inflammatory agent by reducing IL1β secretion accompanied by diminished cellular influx and reduced bacterial dissemination to distant ... |
format |
Article in Journal/Newspaper |
author |
Gavin C K W Koh Tassili A Weehuizen Katrin Breitbach Kathrin Krause Hanna K de Jong Liesbeth M Kager Arjan J Hoogendijk Antje Bast Sharon J Peacock Tom van der Poll Ivo Steinmetz W Joost Wiersinga |
author_facet |
Gavin C K W Koh Tassili A Weehuizen Katrin Breitbach Kathrin Krause Hanna K de Jong Liesbeth M Kager Arjan J Hoogendijk Antje Bast Sharon J Peacock Tom van der Poll Ivo Steinmetz W Joost Wiersinga |
author_sort |
Gavin C K W Koh |
title |
Glyburide reduces bacterial dissemination in a mouse model of melioidosis. |
title_short |
Glyburide reduces bacterial dissemination in a mouse model of melioidosis. |
title_full |
Glyburide reduces bacterial dissemination in a mouse model of melioidosis. |
title_fullStr |
Glyburide reduces bacterial dissemination in a mouse model of melioidosis. |
title_full_unstemmed |
Glyburide reduces bacterial dissemination in a mouse model of melioidosis. |
title_sort |
glyburide reduces bacterial dissemination in a mouse model of melioidosis. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2013 |
url |
https://doi.org/10.1371/journal.pntd.0002500 https://doaj.org/article/2882ae12f52944739cca9b84fe471122 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 7, Iss 10, p e2500 (2013) |
op_relation |
http://europepmc.org/articles/PMC3798430?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0002500 https://doaj.org/article/2882ae12f52944739cca9b84fe471122 |
op_doi |
https://doi.org/10.1371/journal.pntd.0002500 |
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PLoS Neglected Tropical Diseases |
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7 |
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10 |
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e2500 |
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1766346527956008960 |