title: Legionella pneumophila glucosyltransferase inhibits host elongation factor 1A.
abstract: Legionella pneumophila, the causal agent of Legionnaires' disease, is an intracellular parasite and invades and proliferates within different eukaryotic cells, including human alveolar macrophages. After several 100-fold multiplication within host cells, the pathogens are released for new invasion by induction of apoptosis or necrosis. Here we report that L. pneumophila produces a glucosyltransferase, which selectively modifies an approximately 50-kDa mammalian protein by using UDP-glucose as a cosubstrate. MS analysis identified the protein substrate as the mammalian elongation factor (EF)1A. Legionella glucosyltransferase modifies its eukaryotic protein substrate at serine-53, which is located in the GTPase domain of the EF. Glucosylation of EF1A results in inhibition of eukaryotic protein synthesis and death of target cells. Our findings show a mode of inhibition of protein synthesis by microbial pathogens and offer a perspective for understanding of the host-pathogen interaction of L. pneumophila.
authors.affiliation: Gamaleya Research Institute, Ulitsa Gamalei 18, Moscow 123098, Russia.
authors.forename: Yury
authors.initials: Y
authors.lastname: Belyi
authors.forename: Ricarda
authors.initials: R
authors.lastname: Niggeweg
authors.forename: Bastian
authors.initials: B
authors.lastname: Opitz
authors.forename: Martin
authors.initials: M
authors.lastname: Vogelsgesang
authors.forename: Stefan
authors.initials: S
authors.lastname: Hippenstiel
authors.forename: Matthias
authors.initials: M
authors.lastname: Wilm
authors.forename: Klaus
authors.initials: K
authors.lastname: Aktories
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018938:Caco-2 Cells; D002417:Cattle; D002460:Cell Line; D005964:Glucosyltransferases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D016952:Legionella pneumophila / Q000201:enzymology* / Q000235:genetics / Q000472:pathogenicity; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D020648:Peptide Elongation Factor 1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity
chemical_list: D020648:Peptide Elongation Factor 1; D011993:Recombinant Fusion Proteins; D005964:Glucosyltransferases