Eradication of intracellular <it>Francisella tularensis </it>in THP-1 human macrophages with a novel autophagy inducing agent
<p>Abstract</p> <p>Background</p> <p>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 sur...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2009-12-01
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| Series: | Journal of Biomedical Science |
| Online Access: | http://www.jbiomedsci.com/content/16/1/110 |
| Summary: | <p>Abstract</p> <p>Background</p> <p>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 <it>Francisella tularensis</it>, the causative bacterium of tularemia in humans and a potential bioterrorism agent, in macrophages.</p> <p>Methods and results</p> <p>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 <it>F. tularensis </it>(type A strain, Schu S4) and <it>F. novicida </it>in macrophages in association with increased bacterial co-localization with autophagosomes. The effect of AR-12 on intracellular <it>F. novicida </it>was fully reversed in the presence of the autophagy inhibitor, 3-methyl adenine or the lysosome inhibitor, chloroquine. Intracellular <it>F. novicida </it>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.</p> <p>Conclusion</p> <p>Together, AR-12 represents a proof-of-principle that intracellular <it>F. tularensis </it>can be eradicated by small-molecule agents that target innate immunity.</p> |
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| ISSN: | 1021-7770 1423-0127 |