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Stimulation of autophagy suppresses the intracellular survival of Burkholderia pseudomallei in mammalian cell lines

journal contribution
posted on 16.02.2021, 23:00 by Meabh Cullinane, L Gong, X Li, N Lazar-Adler, T Tra, E Wolvetang, M Prescott, JD Boyce, RJ Devenish, B Adler
Burkholderia pseudomallei is the causative agent of melioidosis, a tropical infection of humans and other animals. The bacterium is an intracellular pathogen that can escape from endosomes into the host cytoplasm, where it replicates and infects adjacent cells. We investigated the role played by autophagy in the intracellular survival of B. pseudomallei in phagocytic and non-phagocytic cell lines. Autophagy was induced in response to B. pseudomallei invasion of murine macrophage (RAW 264.7) cells and a proportion of the bacteria co-localized with the autophagy effector protein LC3, a marker for autophagosome formation. Pharmacological stimulation of autophagy in RAW 264.7 and murine embryonic fibroblast (MEF) cell lines resulted in increased co-localization of B. pseudomallei with LC3 while basal levels of co-localization could be abrogated using inhibitors of the autophagic pathway. Furthermore, induction of autophagy decreased the intracellular survival of B. pseudomallei in these cell lines, but bacterial survival was not affected in MEF cell lines deficient in autophagy. Treatment of infected macrophages with chloramphenicol increased the proportion of bacteria within autophagosomes indicating that autophagic evasion is an active process relying on bacterial protein synthesis. Consistent with this hypothesis, we identified a B. pseudomallei type III secreted (TTS) protein, BopA, which plays a role in mediating bacterial evasion of autophagy. We conclude that the autophagic pathway is a component of the innate defense system against invading B. pseudomallei, but which the bacteria can actively evade. However, when autophagy is pharmacologically induced using rapamycin, bacteria are actively sequestered in autophagosomes, ultimately decreasing their survival. ©2008 Landes Bioscience.


We thank Prof N. Mizushima (Tokyo Medical and Dental University, Japan) and Prof T. Yoshimori (National Institute of Genetics, Japan) for providing Atg5-/- MEF cells and the GFP-LC3 construct respectively and Prof P. Hertzog (Monash Institute of Medical Research, Australia) for providing IFN gamma. This work was supported by grants from the Australian Research Council and the National Health and Medical Research Council, Australia.


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(p. 744-753)





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