Positive and Negative Regulation of the Master Metabolic Regulator mTORC1 by Two Families of Legionella pneumophila Effectors
Justin A. De Leon,
Jiazhang Qiu,
Christopher J. Nicolai,
Jessica L. Counihan,
Kevin C. Barry,
Li Xu,
Rosalie E. Lawrence,
Brian M. Castellano,
Roberto Zoncu,
Daniel K. Nomura,
Zhao-Qing Luo,
Russell E. Vance
Affiliations
Justin A. De Leon
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA
Jiazhang Qiu
Purdue Institute for Inflammation, Immunology, and Infectious Disease and Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, USA
Christopher J. Nicolai
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA
Jessica L. Counihan
Department of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA 94720, USA
Kevin C. Barry
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA
Li Xu
Purdue Institute for Inflammation, Immunology, and Infectious Disease and Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, USA
Rosalie E. Lawrence
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA
Brian M. Castellano
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA
Roberto Zoncu
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA
Daniel K. Nomura
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA
Zhao-Qing Luo
Purdue Institute for Inflammation, Immunology, and Infectious Disease and Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, USA
Russell E. Vance
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA
All pathogens must acquire nutrients from their hosts. The intracellular bacterial pathogen Legionella pneumophila, the etiological agent of Legionnaires’ disease, requires host amino acids for growth within cells. The mechanistic target of rapamycin complex 1 (mTORC1) is an evolutionarily conserved master regulator of host amino acid metabolism. Here, we identify two families of translocated L. pneumophila effector proteins that exhibit opposing effects on mTORC1 activity. The Legionella glucosyltransferase (Lgt) effector family activates mTORC1, through inhibition of host translation, whereas the SidE/SdeABC (SidE) effector family acts as mTORC1 inhibitors. We demonstrate that a common activity of both effector families is to inhibit host translation. We propose that the Lgt and SidE families of effectors work in concert to liberate host amino acids for consumption by L. pneumophila.
