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Eradication of intracellular Francisella tularensis in THP-1 human macrophages with a novel autophagy inducing agent
BACKGROUND: Autophagy has been shown recently to play an important role in the intracellular survival of several pathogenic bacteria. In this study, we investigated the effect of a novel small-molecule autophagy-inducing agent, AR-12, on the survival of Francisella tularensis, the causative bacteriu...
Autores principales: | , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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BioMed Central
2009
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2801672/ https://www.ncbi.nlm.nih.gov/pubmed/20003180 http://dx.doi.org/10.1186/1423-0127-16-110 |
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author | Chiu, Hao-Chieh Soni, Shilpa Kulp, Samuel K Curry, Heather Wang, Dasheng Gunn, John S Schlesinger, Larry S Chen, Ching-Shih |
author_facet | Chiu, Hao-Chieh Soni, Shilpa Kulp, Samuel K Curry, Heather Wang, Dasheng Gunn, John S Schlesinger, Larry S Chen, Ching-Shih |
author_sort | Chiu, Hao-Chieh |
collection | PubMed |
description | BACKGROUND: Autophagy has been shown recently to play an important role in the intracellular survival of several pathogenic bacteria. In this study, we investigated the effect of a novel small-molecule autophagy-inducing agent, AR-12, on the survival of Francisella tularensis, the causative bacterium of tularemia in humans and a potential bioterrorism agent, in macrophages. METHODS AND RESULTS: Our results show that AR-12 induces autophagy in THP-1 macrophages, as indicated by increased autophagosome formation, and potently inhibits the intracellular survival of F. tularensis (type A strain, Schu S4) and F. novicida in macrophages in association with increased bacterial co-localization with autophagosomes. The effect of AR-12 on intracellular F. novicida was fully reversed in the presence of the autophagy inhibitor, 3-methyl adenine or the lysosome inhibitor, chloroquine. Intracellular F. novicida were not susceptible to the inhibitory activity of AR-12 added at 12 h post-infection in THP-1 macrophages, and this lack of susceptibility was independent of the intracellular location of bacteria. CONCLUSION: Together, AR-12 represents a proof-of-principle that intracellular F. tularensis can be eradicated by small-molecule agents that target innate immunity. |
format | Text |
id | pubmed-2801672 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-28016722010-01-05 Eradication of intracellular Francisella tularensis in THP-1 human macrophages with a novel autophagy inducing agent Chiu, Hao-Chieh Soni, Shilpa Kulp, Samuel K Curry, Heather Wang, Dasheng Gunn, John S Schlesinger, Larry S Chen, Ching-Shih J Biomed Sci Research BACKGROUND: Autophagy has been shown recently to play an important role in the intracellular survival of several pathogenic bacteria. In this study, we investigated the effect of a novel small-molecule autophagy-inducing agent, AR-12, on the survival of Francisella tularensis, the causative bacterium of tularemia in humans and a potential bioterrorism agent, in macrophages. METHODS AND RESULTS: Our results show that AR-12 induces autophagy in THP-1 macrophages, as indicated by increased autophagosome formation, and potently inhibits the intracellular survival of F. tularensis (type A strain, Schu S4) and F. novicida in macrophages in association with increased bacterial co-localization with autophagosomes. The effect of AR-12 on intracellular F. novicida was fully reversed in the presence of the autophagy inhibitor, 3-methyl adenine or the lysosome inhibitor, chloroquine. Intracellular F. novicida were not susceptible to the inhibitory activity of AR-12 added at 12 h post-infection in THP-1 macrophages, and this lack of susceptibility was independent of the intracellular location of bacteria. CONCLUSION: Together, AR-12 represents a proof-of-principle that intracellular F. tularensis can be eradicated by small-molecule agents that target innate immunity. BioMed Central 2009-12-09 /pmc/articles/PMC2801672/ /pubmed/20003180 http://dx.doi.org/10.1186/1423-0127-16-110 Text en Copyright ©2009 Chiu et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Chiu, Hao-Chieh Soni, Shilpa Kulp, Samuel K Curry, Heather Wang, Dasheng Gunn, John S Schlesinger, Larry S Chen, Ching-Shih Eradication of intracellular Francisella tularensis in THP-1 human macrophages with a novel autophagy inducing agent |
title | Eradication of intracellular Francisella tularensis in THP-1 human macrophages with a novel autophagy inducing agent |
title_full | Eradication of intracellular Francisella tularensis in THP-1 human macrophages with a novel autophagy inducing agent |
title_fullStr | Eradication of intracellular Francisella tularensis in THP-1 human macrophages with a novel autophagy inducing agent |
title_full_unstemmed | Eradication of intracellular Francisella tularensis in THP-1 human macrophages with a novel autophagy inducing agent |
title_short | Eradication of intracellular Francisella tularensis in THP-1 human macrophages with a novel autophagy inducing agent |
title_sort | eradication of intracellular francisella tularensis in thp-1 human macrophages with a novel autophagy inducing agent |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2801672/ https://www.ncbi.nlm.nih.gov/pubmed/20003180 http://dx.doi.org/10.1186/1423-0127-16-110 |
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