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Autophagosomes can support Yersinia pseudotuberculosis replication in macrophages.
Cell Microbiol. 2010 Aug; 12(8):1108-23
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12 Aug 2010
New Finding
DOI: 10.3410/f.4671961.4550064
In this study, the authors show how autophagy, a degradative pathway, can be hijacked by a bacterium, Yersinia pseudotuberculosis, to promote its survival inside macrophages. The main finding is that the Y. pseudotuberculosis-containing vacuole intersects with the autophagy pathway in macrophages but...Continue reading
In this study, the authors show how autophagy, a degradative pathway, can be hijacked by a bacterium, Yersinia pseudotuberculosis, to promote its survival inside macrophages. The main finding is that the Y. pseudotuberculosis-containing vacuole intersects with the autophagy pathway in macrophages but bacteria are able to manipulate autophagy to survive and replicate in their host.
First, using electron microscopy of infected macrophages, Moreau et al. observed Y. pseudotuberculosis in a vacuole surrounded by multiple membranes. The authors suggested this structure to be an autophagosome, a compartment that usually captures various cytoplasmic components and undergoes maturation leading to fusion with lysosomes and degradation of its content. The authors then provide convincing evidence of an interaction of the Yersinia vacuole with autophagy, as it for example recruits the classical marker LC3/Atg8. At this stage, the authors developed elegant techniques to determine the physiological status of the bacteria in their vacuoles and demonstrated that, upon autophagy induction, Yersinia remains metabolically active and even replicates inside the generated compartment. The authors show that the bacteria hijack and block the autophagy pathway to create a favorable compartment that does not acidify and where they can survive. Interestingly, the authors present evidence that autophagy is needed to maintain this favorable environment as inhibition of autophagy is associated with trafficking of the bacteria to an acidic vacuole. The bacterial effectors involved in this mechanism remain to be identified and may be shared with Yersinia pestis, the plague bacillus that emerged from and is closely related to Y. pseudotuberculosis. Indeed, Y. pestis is also able to replicate in an autophagosome and inhibition of autophagy leads to the trafficking of the bacterium to an acidic compartment {1}.
First, using electron microscopy of infected macrophages, Moreau et al. observed Y. pseudotuberculosis in a vacuole surrounded by multiple membranes. The authors suggested this structure to be an autophagosome, a compartment that usually captures various cytoplasmic components and undergoes maturation leading to fusion with lysosomes and degradation of its content. The authors then provide convincing evidence of an interaction of the Yersinia vacuole with autophagy, as it for example recruits the classical marker LC3/Atg8. At this stage, the authors developed elegant techniques to determine the physiological status of the bacteria in their vacuoles and demonstrated that, upon autophagy induction, Yersinia remains metabolically active and even replicates inside the generated compartment. The authors show that the bacteria hijack and block the autophagy pathway to create a favorable compartment that does not acidify and where they can survive. Interestingly, the authors present evidence that autophagy is needed to maintain this favorable environment as inhibition of autophagy is associated with trafficking of the bacteria to an acidic vacuole. The bacterial effectors involved in this mechanism remain to be identified and may be shared with Yersinia pestis, the plague bacillus that emerged from and is closely related to Y. pseudotuberculosis. Indeed, Y. pestis is also able to replicate in an autophagosome and inhibition of autophagy leads to the trafficking of the bacterium to an acidic compartment {1}.
References
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Yersinia pestis can reside in autophagosomes and avoid xenophagy in murine macrophages by preventing vacuole acidification.
Infect Immun 2009 Jun; 6(77):2251-61
PMID: 19289509
Disclosures
None declared
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Soldati T and Arafah S: F1000Prime Recommendation of [Moreau K et al., Cell Microbiol 2010, 12(8):1108-23]. In F1000Prime, 12 Aug 2010; DOI: 10.3410/f.4671961.4550064. F1000Prime.com/4671961#eval4550064
F1000Prime Recommendations, Dissents and Comments for [Moreau K et al., Cell Microbiol 2010, 12(8):1108-23]. In F1000Prime, 19 May 2013; F1000Prime.com/4671961
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Yersinia pseudotuberculosis is able to replicate inside macrophages. However, the intracellular trafficking of the pathogen after its entry into the macrophage remains poorly understood. Using in vitro infected bone marrow-derived macrophages, we show that Y. pseudotuberculosis activates the autophagy pathway. Host cell autophagosomes subverted by bacteria do not become acidified and sustain bacteria replication. Moreover, we report that autophagy inhibition correlated with bacterial trafficking inside an acidic compartment. This study indicates that Y. pseudotuberculosis hijacks the autophagy pathway for its replication and also opens up new opportunities for deciphering the molecular basis of the host cell signalling response to intracellular Yersinia infection.
DOI: 10.1111/j.1462-5822.2010.01456.x
PMID: 20180800
