Legionella pneumophila Glucosyltransferase Inhibits Host Elongation Factor 1A
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 invas...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2006-11, Vol.103 (45), p.16953-16958 |
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| container_issue | 45 |
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| container_title | Proceedings of the National Academy of Sciences - PNAS |
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| creator | Belyi, Yury Niggeweg, Ricarda Opitz, Bastian Vogelsgesang, Martin Hippenstiel, Stefan Wilm, Matthias Aktories, Klaus |
| description | 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. |
| doi_str_mv | 10.1073/pnas.0601562103 |
| format | Article |
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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.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.0601562103</identifier><identifier>PMID: 17068130</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>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</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2006-11, Vol.103 (45), p.16953-16958</ispartof><rights>Copyright 2006 National Academy of Sciences of the United States of America</rights><rights>Copyright National Academy of Sciences Nov 7, 2006</rights><rights>2006 by The National Academy of Sciences of the USA 2006</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c530t-41eaa4deca4625c276ac65077de8a669373e8c143eee1658030d742098d3a3c23</citedby><cites>FETCH-LOGICAL-c530t-41eaa4deca4625c276ac65077de8a669373e8c143eee1658030d742098d3a3c23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/103/45.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/30051776$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/30051776$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,727,780,784,803,885,27924,27925,53791,53793,58017,58250</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17068130$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Belyi, Yury</creatorcontrib><creatorcontrib>Niggeweg, Ricarda</creatorcontrib><creatorcontrib>Opitz, Bastian</creatorcontrib><creatorcontrib>Vogelsgesang, Martin</creatorcontrib><creatorcontrib>Hippenstiel, Stefan</creatorcontrib><creatorcontrib>Wilm, Matthias</creatorcontrib><creatorcontrib>Aktories, Klaus</creatorcontrib><title>Legionella pneumophila Glucosyltransferase Inhibits Host Elongation Factor 1A</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>Legionella pneumophila, the causal agent of Legionnaires' disease, is an intracellular parasite and invades and proliferates within different eukaryotic cells, including human alveolar macrophages. 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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.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>17068130</pmid><doi>10.1073/pnas.0601562103</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| 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 |
| title | Legionella pneumophila Glucosyltransferase Inhibits Host Elongation Factor 1A |
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