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Cellular Microbiology: Pathogen-Host Cell Molecular Interactions | Spotlight

Legionella pneumophila Excludes Autophagy Adaptors from the Ubiquitin-Labeled Vacuole in Which It Resides

Titilayo O. Omotade, Craig R. Roy
Igor E. Brodsky, Editor
Titilayo O. Omotade
aDepartment of Microbial Pathogenesis, Yale University School of Medicine, Boyer Center for Molecular Medicine, New Haven, Connecticut, USA
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Craig R. Roy
aDepartment of Microbial Pathogenesis, Yale University School of Medicine, Boyer Center for Molecular Medicine, New Haven, Connecticut, USA
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Igor E. Brodsky
University of Pennsylvania
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DOI: 10.1128/IAI.00793-19
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ABSTRACT

Xenophagy targets intracellular pathogens for destruction by the host autophagy pathway. Ubiquitin chains are conjugated to xenophagic targets and recruit multiple autophagy adaptors. The intracellular pathogen Legionella pneumophila resides in a vacuole that is ubiquitinated; however, this pathogen avoids xenophagic detection. Here, the mechanisms by which L. pneumophila can prevent the host xenophagy pathway from targeting the vacuole in which it resides were examined. Ubiquitin-labeled vacuoles containing L. pneumophila failed to recruit autophagy adaptors by a process that was independent of RavZ function. Coinfection studies were conducted using a strain of Listeria monocytogenes that served as a robust xenophagic target. Legionella pneumophila infection blocked xenophagic targeting of L. monocytogenes by a RavZ-dependent mechanism. Importantly, when coinfection studies were conducted with a RavZ-deficient strain of L. pneumophila, L. monocytogenes was targeted by the host xenophagy system but vacuoles containing L. pneumophila avoided targeting. Enhanced adaptor recruitment to the vacuole was observed by using a strain of L. pneumophila in which all of the effector proteins in the SidE family were deleted; however, this strain was still not targeted by the host autophagy pathway. Thus, there are at least two pathways by which L. pneumophila can disrupt xenophagic targeting of the vacuole in which it resides. One mechanism involves global disruption of the host autophagy machinery by the effector protein RavZ. A second cis-acting mechanism prevents the binding of autophagy adaptors to the ubiquitin-decorated surface of the L. pneumophila-containing vacuole.

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Legionella pneumophila Excludes Autophagy Adaptors from the Ubiquitin-Labeled Vacuole in Which It Resides
Titilayo O. Omotade, Craig R. Roy
Infection and Immunity Jul 2020, 88 (8) e00793-19; DOI: 10.1128/IAI.00793-19

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Legionella pneumophila Excludes Autophagy Adaptors from the Ubiquitin-Labeled Vacuole in Which It Resides
Titilayo O. Omotade, Craig R. Roy
Infection and Immunity Jul 2020, 88 (8) e00793-19; DOI: 10.1128/IAI.00793-19
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KEYWORDS

Legionella pneumophila
autophagy
bacterial effector proteins
type IV secretion

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