title: Host proteasomal degradation generates amino acids essential for intracellular bacterial growth.
abstract: Legionella pneumophila proliferates in environmental amoeba and human cells within the Legionella-containing vacuole (LCV). The exported AnkB F-box effector of L. pneumophila is anchored into the LCV membrane by host-mediated farnesylation. Here, we report that host proteasomal degradation of Lys(48)-linked polyubiquitinated proteins, assembled on the LCV by AnkB, generates amino acids required for intracellular bacterial proliferation. The severe defect of the ankB null mutant in proliferation within amoeba and human cells is rescued by supplementation of a mixture of amino acids or cysteine, serine, pyruvate, or citrate, similar to rescue by genetic complementation. Defect of the ankB mutant in intrapulmonary proliferation in mice is rescued upon injection of a mixture of amino acids or cysteine. Therefore, Legionella promotes eukaryotic proteasomal degradation to generate amino acids needed as carbon and energy sources for bacterial proliferation within evolutionarily distant hosts.
authors.affiliation: Department of Microbiology and Immunology, College of Medicine, University of Louisville, KY 40202, USA.
authors.forename: Christopher T D
authors.initials: CT
authors.lastname: Price
authors.forename: Tasneem
authors.initials: T
authors.lastname: Al-Quadan
authors.forename: Marina
authors.initials: M
authors.lastname: Santic
authors.forename: Ilan
authors.initials: I
authors.lastname: Rosenshine
authors.forename: Yousef
authors.initials: Y
authors.lastname: Abu Kwaik
mesh_terms: D000048:Acanthamoeba / Q000382:microbiology; D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D049109:Cell Proliferation; D044783:F-Box Proteins / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D016952:Legionella pneumophila / Q000254:growth & development* / Q000378:metabolism*; D007877:Legionnaires' Disease / Q000378:metabolism / Q000382:microbiology; D008239:Lysine / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D025801:Ubiquitin / Q000235:genetics / Q000378:metabolism; D057149:Ubiquitinated Proteins / Q000378:metabolism; D014617:Vacuoles / Q000378:metabolism / Q000382:microbiology
chemical_list: D000596:Amino Acids; D044783:F-Box Proteins; D025801:Ubiquitin; D057149:Ubiquitinated Proteins; D046988:Proteasome Endopeptidase Complex; D008239:Lysine