- 作者: Hao-Chieh Chiu; Shilpa Soni; Samuel K Kulp; Heather Curry; Dasheng Wang; John S Gunn; Larry S Schlesinger; Ching-Shih Chen
- 中文摘要: --
- 英文摘要:
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 smallmolecule
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. - 中文關鍵字: --
- 英文關鍵字: --