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  Screening for eukaryotic motifs in Legionella pneumophila reveals Smh1 as bacterial deacetylase of host histones

Herbel, S. M., Moyon, L., Christ, M., Elsayed, E. M., Caffrey, B. E., Malmsheimer, S., Grin, I., Hoffmann, K., Surmann, K., Blankenburg, S., Jung, A. L., Herkt, C. E., Borsò, M., Bozdag, B., Imhof, A., Becker, A., Wagner, S., Bange, G., Völker, U., Bertrams, W., Marsico, A., & Schmeck, B. (2022). Screening for eukaryotic motifs in Legionella pneumophila reveals Smh1 as bacterial deacetylase of host histones. Virulence, 13(1), 2042-2058. doi:10.1080/21505594.2022.2149973.

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アイテムのパーマリンク: https://hdl.handle.net/21.11116/0000-000B-B269-6 版のパーマリンク: https://hdl.handle.net/21.11116/0000-000E-3CB7-1
資料種別: 学術論文

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 作成者:
Herbel, S. M., 著者
Moyon, L., 著者
Christ, M., 著者
Elsayed, E. M., 著者
Caffrey, B. E., 著者
Malmsheimer, S., 著者
Grin, I., 著者
Hoffmann, K., 著者
Surmann, K., 著者
Blankenburg, S., 著者
Jung, A. L., 著者
Herkt, C. E., 著者
Borsò, M., 著者
Bozdag, B., 著者
Imhof, A., 著者
Becker, A., 著者
Wagner, S., 著者
Bange, G.1, 2, 3, 著者                 
Völker, U., 著者
Bertrams, W., 著者
Marsico, A., 著者Schmeck, B., 著者 全て表示
所属:
1Max Planck Fellow Molecular Physiology of Microbes, Max Planck Institute for Terrestrial Microbiology, Max Planck Society, ou_3321791              
2Philipps-Universität Marburg, Department Chemistry, ou_persistent22              
3Philipps-Universität Marburg, Center for Synthetic Microbiology, ou_persistent22              

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キーワード: Humans *Eukaryota Histones/genetics *Legionella pneumophila/genetics Eukaryotic Cells Research Virulence Factors/genetics Histone Deacetylases Repressor Proteins Infection Legionella pneumophila Smh1 histone-deacetylase macrophage
 要旨: Legionella pneumophila (L.p.) is a bacterial pathogen which is a common causative agent of pneumonia. In humans, it infects alveolar macrophages and transfers hundreds of virulence factors that interfere with cellular signalling pathways and the transcriptomic landscape to sustain its own replication. By this interaction, it has acquired eukaryote-like protein motifs by gene transfer events that partake in the pathogenicity of Legionella. In a computational screening approach for eukaryotic motifs in the transcriptome of Legionella, we identified the L.p. strain Corby protein ABQ55614 as putative histone-deacetylase and named it "suppressing modifier of histones 1" (Smh1). During infection, Smh1 is translocated from the Legionella vacuole into the host cytosol. When expressed in human macrophage THP-1 cells, Smh1 was localized predominantly in the nucleus, leading to broad histone H3 and H4 deacetylation, blunted expression of a large number of genes (e.g. IL-1β and IL-8), and fostered intracellular bacterial replication. L.p. with a Smh1 knockdown grew normally in media but showed a slight growth defect inside the host cell. Furthermore, Smh1 showed a very potent histone deacetylation activity in vitro, e.g. at H3K14, that could be inhibited by targeted mutation of the putative catalytic center inferred by analogy with eukaryotic HDAC8, and with the deacetylase inhibitor trichostatin A. In summary, Smh1 displays functional homology with class I/II type HDACs. We identified Smh1 as a new Legionella virulence factor with a eukaryote-like histone-deacetylase activity that moderates host gene expression and might pave the way for further histone modifications.IMPORTANCELegionella pneumophila (L.p.) is a prominent bacterial pathogen, which is a common causative agent of pneumonia. In order to survive inside the host cell, the human macrophage, it profoundly interacts with host cell processes to advance its own replication. In this study, we identify a bacterial factor, Smh1, with yet unknown function as a host histone deacetylase. The activity of this factor in the host cell leads to attenuated gene expression and increased intracellular bacterial replication.

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言語: eng - English
 日付: 2022-11-22
 出版の状態: 出版
 ページ: -
 出版情報: -
 目次: -
 査読: 査読あり
 識別子(DOI, ISBNなど): その他: 36411449
DOI: 10.1080/21505594.2022.2149973
ISSN: 2150-5594 (Print)2150-5594
 学位: -

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出版物 1

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出版物名: Virulence
種別: 学術雑誌
 著者・編者:
所属:
出版社, 出版地: Landes Bioscience
ページ: - 巻号: 13 (1) 通巻号: - 開始・終了ページ: 2042 - 2058 識別子(ISBN, ISSN, DOIなど): ISSN: 2150-5608
CoNE: https://pure.mpg.de/cone/journals/resource/2150-5608