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Survival and Trafficking of Yersinia pestis in Non-acidified Phagosomes in Murine Macrophages

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The Challenge of Highly Pathogenic Microorganisms

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Abstract

Yersinia pestis is a facultative intracellular bacterial pathogen. Survival of Y. pestis in macrophages is thought to play an important role in pathogenesis during the earliest stages of plague. Recent studies have identified several bacterial genes important for survival in macrophages, and determined that Y. pestis inhabits a compartment called the Yersinia-containing vacuole (YCV), which acquires markers of late endosomes or lysosomes. Furthermore, studies have shown the ability of Y. pestis to survive in macrophages activated with the cytokine IFNγ. Some vacuolar pathogens appear to co-opt the process of autophagy for survival in host cells. Alternatively, xenophagy is an autophagic process that is upregulated in activated macrophages and functions to kill bacteria in acidic autophagosomes. Studies were undertaken to investigate the mechanism of Y. pestis survival in phagosomes of naïve and activated macrophages, and to determine if the pathogen avoids or co-opts autophagy. Co-localization of the YCV with markers of autophagosomes or acidic lysosomes, and the pH of the YCV, was determined by microscopic imaging of infected macrophages. Results showed that YCVs could contain double membranes characteristic of autophagosomes and co-localized with a marker of autophagic membranes. Interestingly, YCVs failed to acidify below pH of 7. In addition, Y. pestis survived equally well in macrophages proficient or deficient for autophagy, showing that the bacterium does not co-opt autophagy for intracellular survival. It is concluded that although Y. pestis can reside in autophagosomes, the pathogen avoids destruction by xenophagy by preventing vacuole acidification. Y. pestis may actively prevent phagosome acidification in either naïve or activated macrophages by preventing delivery of the vacuolar ATPase (vATPase) to the YCV or direct inactivation of the vATPase.

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Acknowledgements

I thank Kate Klein for permission to cite unpublished data. The work summarized in this chapter was supported by grants from the NIH awarded to J.B.B. (PO1-AI055621 and the Northeast Biodefense Center U54-AI057158-Lipkin).

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  1. Center for Infectious Diseases and Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, NY, 11794, USA

    James B. Bliska

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  1. James B. Bliska
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Correspondence to James B. Bliska .

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  1. Israel Institute for Biological Research, Ness-Ziona, 74100, Israel

    Avigdor Shafferman

  2. Israel Institute for Biological Research, P.O. Box 19, Ness-Ziona, 74100, Israel

    Arie Ordentlich

  3. Israel Institute for Biological Research, P.O. Box 19, Ness-Ziona, 74100, Israel

    Baruch Velan

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Bliska, J.B. (2010). Survival and Trafficking of Yersinia pestis in Non-acidified Phagosomes in Murine Macrophages. In: Shafferman, A., Ordentlich, A., Velan, B. (eds) The Challenge of Highly Pathogenic Microorganisms. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-9054-6_4

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