Post-exposure therapeutic efficacy of COX-2 inhibition against Burkholderia pseudomallei.
Burkholderia pseudomallei is a Gram-negative, facultative intracellular bacillus and the etiologic agent of melioidosis, a severe disease in Southeast Asia and Northern Australia. Like other multidrug-resistant pathogens, the inherent antibiotic resistance of B. pseudomallei impedes treatment and hi...
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ftdoajarticles:oai:doaj.org/article:b216055128c349bf991bd8ce5f76f353 2023-05-15T15:05:15+02:00 Post-exposure therapeutic efficacy of COX-2 inhibition against Burkholderia pseudomallei. Saja Asakrah Wildaliz Nieves Zaid Mahdi Mallory Agard Arnold H Zea Chad J Roy Lisa A Morici 2013-01-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0002212 https://doaj.org/article/b216055128c349bf991bd8ce5f76f353 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC3649956?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0002212 https://doaj.org/article/b216055128c349bf991bd8ce5f76f353 PLoS Neglected Tropical Diseases, Vol 7, Iss 5, p e2212 (2013) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2013 ftdoajarticles https://doi.org/10.1371/journal.pntd.0002212 2023-01-08T01:28:20Z Burkholderia pseudomallei is a Gram-negative, facultative intracellular bacillus and the etiologic agent of melioidosis, a severe disease in Southeast Asia and Northern Australia. Like other multidrug-resistant pathogens, the inherent antibiotic resistance of B. pseudomallei impedes treatment and highlights the need for alternative therapeutic strategies that can circumvent antimicrobial resistance mechanisms. In this work, we demonstrate that host prostaglandin E2 (PGE2) production plays a regulatory role in the pathogenesis of B. pseudomallei. PGE2 promotes B. pseudomallei intracellular survival within macrophages and bacterial virulence in a mouse model of pneumonic melioidosis. PGE2-mediated immunosuppression of macrophage bactericidal effector functions is associated with increased arginase 2 (Arg2) expression and decreased nitric oxide (NO) production. Treatment with a commercially-available COX-2 inhibitor suppresses the growth of B. pseudomallei in macrophages and affords significant protection against rapidly lethal pneumonic melioidosis when administered post-exposure to B. pseudomallei-infected mice. COX-2 inhibition may represent a novel immunotherapeutic strategy to control infection with B. pseudomallei and other intracellular pathogens. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLoS Neglected Tropical Diseases 7 5 e2212 |
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Directory of Open Access Journals: DOAJ Articles |
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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 Saja Asakrah Wildaliz Nieves Zaid Mahdi Mallory Agard Arnold H Zea Chad J Roy Lisa A Morici Post-exposure therapeutic efficacy of COX-2 inhibition against Burkholderia pseudomallei. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Burkholderia pseudomallei is a Gram-negative, facultative intracellular bacillus and the etiologic agent of melioidosis, a severe disease in Southeast Asia and Northern Australia. Like other multidrug-resistant pathogens, the inherent antibiotic resistance of B. pseudomallei impedes treatment and highlights the need for alternative therapeutic strategies that can circumvent antimicrobial resistance mechanisms. In this work, we demonstrate that host prostaglandin E2 (PGE2) production plays a regulatory role in the pathogenesis of B. pseudomallei. PGE2 promotes B. pseudomallei intracellular survival within macrophages and bacterial virulence in a mouse model of pneumonic melioidosis. PGE2-mediated immunosuppression of macrophage bactericidal effector functions is associated with increased arginase 2 (Arg2) expression and decreased nitric oxide (NO) production. Treatment with a commercially-available COX-2 inhibitor suppresses the growth of B. pseudomallei in macrophages and affords significant protection against rapidly lethal pneumonic melioidosis when administered post-exposure to B. pseudomallei-infected mice. COX-2 inhibition may represent a novel immunotherapeutic strategy to control infection with B. pseudomallei and other intracellular pathogens. |
format |
Article in Journal/Newspaper |
author |
Saja Asakrah Wildaliz Nieves Zaid Mahdi Mallory Agard Arnold H Zea Chad J Roy Lisa A Morici |
author_facet |
Saja Asakrah Wildaliz Nieves Zaid Mahdi Mallory Agard Arnold H Zea Chad J Roy Lisa A Morici |
author_sort |
Saja Asakrah |
title |
Post-exposure therapeutic efficacy of COX-2 inhibition against Burkholderia pseudomallei. |
title_short |
Post-exposure therapeutic efficacy of COX-2 inhibition against Burkholderia pseudomallei. |
title_full |
Post-exposure therapeutic efficacy of COX-2 inhibition against Burkholderia pseudomallei. |
title_fullStr |
Post-exposure therapeutic efficacy of COX-2 inhibition against Burkholderia pseudomallei. |
title_full_unstemmed |
Post-exposure therapeutic efficacy of COX-2 inhibition against Burkholderia pseudomallei. |
title_sort |
post-exposure therapeutic efficacy of cox-2 inhibition against burkholderia pseudomallei. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2013 |
url |
https://doi.org/10.1371/journal.pntd.0002212 https://doaj.org/article/b216055128c349bf991bd8ce5f76f353 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 7, Iss 5, p e2212 (2013) |
op_relation |
http://europepmc.org/articles/PMC3649956?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0002212 https://doaj.org/article/b216055128c349bf991bd8ce5f76f353 |
op_doi |
https://doi.org/10.1371/journal.pntd.0002212 |
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PLoS Neglected Tropical Diseases |
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7 |
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5 |
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e2212 |
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