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Dynamic Proteomics Profiling of Legionella pneumophila Infection Unveils Modulation of the Host Mitochondrial Stress Response Pathway

45 Pages Posted: 13 Jul 2020 Publication Status: Review Complete

See all articles by Julia Noack

Julia Noack

University of California, San Francisco (UCSF) - Department of Microbiology and Immunology

David Jimenez-Morales

Gladstone Institute of Data Science and Biotechnology

Erica Stevenson

Gladstone Institute of Data Science and Biotechnology

Tom Moss

University of California, San Francisco (UCSF) - Department of Microbiology and Immunology

Gwendolyn Jang

University of California, San Francisco (UCSF) - Quantitative Biosciences Institute; QBI Coronavirus Research Group (QCRG); University of California, San Francisco (UCSF) - Department of Cellular and Molecular Pharmacology; Gladstone Institutes - Gladstone Institute of Data Science and Biotechnology

Nevan J. Krogan

University of California, San Francisco (UCSF) - Department of Cellular and Molecular Pharmacology; University of California, San Francisco (UCSF) - Institute for Quantitative Biosciences (QB3)

Danielle L. Swaney

Gladstone Institute of Data Science and Biotechnology

Shaeri Mukherjee

University of California, San Francisco (UCSF) - Department of Microbiology and Immunology

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Abstract

The human pathogen Legionella pneumophila (L.p.) secretes ~330 bacterial effector proteins into the host cell which interfere with numerous cellular pathways and often regulate host cell proteins through post-translational modifications. However, the cellular targets and functions of most L.p. effectors are not known. In order to obtain a global overview of potential targets of these effectors, we analyzed the host cell proteome, ubiquitinome, and phosphoproteome during L.p. infection. Our analysis reveals dramatic spatiotemporal changes in the host cell proteome that are dependent on the secretion of bacterial effectors. Strikingly, we show that L.p. substantially reshapes the mitochondrial proteome and modulates mitochondrial stress response pathways such as the mitochondrial unfolded protein response (UPRmt). To our knowledge, this is the first evidence of manipulation of the UPRmt by a bacterial pathogen in mammalian cells. In addition, we have identified a previously uncharacterized L.p. effector that is targeted to host cell mitochondria and protects mitochondrial network integrity during mitochondrial stress.

Keywords: Legionella pneumophila, Bacterial effectors, proteomics, Phosphoproteome, ubiquitinome, Host-pathogen interaction, mitochondrial stress, UPRmt, proteostasis, integrated stress response, Mitochondrial dynamics

Suggested Citation

Noack, Julia and Jimenez-Morales, David and Stevenson, Erica and Moss, Tom and Jang, Gwendolyn and Krogan, Nevan J. and Swaney, Danielle L. and Mukherjee, Shaeri, Dynamic Proteomics Profiling of Legionella pneumophila Infection Unveils Modulation of the Host Mitochondrial Stress Response Pathway. Available at SSRN: https://ssrn.com/abstract=3631502 or http://dx.doi.org/10.2139/ssrn.3631502
This version of the paper has not been formally peer reviewed.

Julia Noack

University of California, San Francisco (UCSF) - Department of Microbiology and Immunology ( email )

San Francisco, CA 94143
United States

David Jimenez-Morales

Gladstone Institute of Data Science and Biotechnology ( email )

1650 OWENS STREET
San Francisco, CA 94158
United States

Erica Stevenson

Gladstone Institute of Data Science and Biotechnology ( email )

1650 OWENS STREET
San Francisco, CA 94158
United States

Tom Moss

University of California, San Francisco (UCSF) - Department of Microbiology and Immunology ( email )

San Francisco, CA 94143
United States

Gwendolyn Jang

University of California, San Francisco (UCSF) - Quantitative Biosciences Institute ( email )

Third Avenue and Parnassus
San Francisco, CA 94158
United States

QBI Coronavirus Research Group (QCRG) ( email )

San Francisco, CA 94158
United States

University of California, San Francisco (UCSF) - Department of Cellular and Molecular Pharmacology ( email )

San Francisco, CA
United States

Gladstone Institutes - Gladstone Institute of Data Science and Biotechnology ( email )

Nevan J. Krogan

University of California, San Francisco (UCSF) - Department of Cellular and Molecular Pharmacology

San Francisco, CA
United States

University of California, San Francisco (UCSF) - Institute for Quantitative Biosciences (QB3)

Third Avenue and Parnassus
San Francisco, CA 94143
United States

Danielle L. Swaney

Gladstone Institute of Data Science and Biotechnology ( email )

1650 OWENS STREET
San Francisco, CA 94158
United States

Shaeri Mukherjee (Contact Author)

University of California, San Francisco (UCSF) - Department of Microbiology and Immunology ( email )

San Francisco, CA 94143
United States

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