Legionella pneumophila Glucosyltransferase Inhibits Host Elongation Factor 1A

• Published in: Proceedings of the National Academy of Sciences - PNAS 2006-11, Vol.103 (45), p.16953-16958
• Main Authors: Belyi, Yury, Niggeweg, Ricarda, Opitz, Bastian, Vogelsgesang, Martin, Hippenstiel, Stefan, Wilm, Matthias, Aktories, Klaus
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Biological Sciences; Caco 2 cells; Cattle; Cell growth; Cell Line; Electroporation; Enzymes; Epithelial cells; Eukaryotes; Eukaryotic cells; Glucosyltransferases - genetics; Glucosyltransferases - metabolism; Humans; In Vitro Techniques; Infections; Legionella; Legionella pneumophila; Legionella pneumophila - enzymology; Legionella pneumophila - genetics; Legionella pneumophila - pathogenicity; Legionnaire's disease; Legionnaires' disease; Mammals; Molecular Sequence Data; Mutagenesis, Site-Directed; Parasite hosts; Parasites; Pathogens; Peptide Elongation Factor 1 - antagonists & inhibitors; Peptide Elongation Factor 1 - genetics; Peptide Elongation Factor 1 - metabolism; Protein synthesis; Rabbits; Recombinant Fusion Proteins - antagonists & inhibitors; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - metabolism; Sequence Homology, Amino Acid; Substrate Specificity; Toxins
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0601562103

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 ᅈ50-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.