A Legionella effector modulates host cytoskeletal structure by inhibiting actin polymerization |
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| Institution: | 1. State Key Laboratory of Agrobiotechnology, Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, and College of Veterinary Medicine, China Agricultural University, Beijing 100193, China;2. Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, USA;1. Boston Children’s Hospital, Boston, MA, USA;2. Massachusetts Institute of Technology, Cambridge, MA, USA;1. Hefei National Laboratory for Physical Sciences at Microscale, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, 230026, China;2. Institute of Physical Science and Information Technology, Department of Chemistry, Anhui University, Hefei, 230601, Anhui, China;3. NewLink Genetics, 2503 S. Loop Drive, Suite 5100, Ames, IA, 50010, USA;1. Department of Chemistry, Chair of Organic Chemistry II, Center for Integrated Protein Science (CIPSM), Technische Universität München, Lichtenbergstraße 4, 85748 Garching, Germany;2. Max Planck Institute of Psychiatry, Kraepelinstraße 2, 80804 München, Germany;3. Department of Chemistry, Ludwig-Maximilians-Universität München, Butenandtstraße 5–13, 81377 München, Germany;1. Institut Pasteur, Biologie des Bactéries Intracellulaires, Paris, France;2. Centre National de la Recherche Scientifique (CNRS) Unité Mixte de Recherche (UMR) 3525, Paris, France;3. Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China;4. Key Laboratory of Innate Immune Biology of Fujian Province, Provincial University Key Laboratory of Cellular Stress Response and Metabolic Regulation, Biomedical Research Center of South China, Key Laboratory of OptoElectronic Science and Technology for Medicine of the Ministry of Education, College of Life Sciences, Fujian Normal University, Fuzhou, China;5. Laboratory for Marine Biology and Biotechnology, Pilot National Laboratory for Marine Science and Technology, Qingdao 266237, China;6. Purdue Institute for Inflammation, Immunology and Infectious Disease and Department of Biological Sciences, Purdue University, West Lafayette, Indiana 47907;12. Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Wuhan University, Wuhan 430072, China |
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| Abstract: | Successful infection by the opportunistic pathogen Legionella pneumophila requires the collective activity of hundreds of virulence proteins delivered into the host cell by the Dot/Icm type IV secretion system. These virulence proteins, also called effectors modulate distinct host cellular processes to create a membrane-bound niche called the Legionella containing vacuole (LCV) supportive of bacterial growth. We found that Ceg14 (Lpg0437), a Dot/Icm substrate is toxic to yeast and such toxicity can be alleviated by overexpression of profilin, a protein involved in cytoskeletal structure in eukaryotes. We further showed that mutations in profilin affect actin binding but not other functions such as interactions with poly-l-proline or phosphatidylinositol, abolish its suppressor activity. Consistent with the fact the profilin suppresses its toxicity, expression of Ceg14 but not its non-toxic mutants in yeast affects actin distribution and budding of daughter cells. Although Ceg14 does not detectably interact with profilin, it co-sediments with filamentous actin and inhibits actin polymerization, causing the accumulation of short actin filaments. Together with earlier studies, these results reveal that multiple L. pneumophila effectors target components of the host cytoskeleton. |
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| Keywords: | Profilin Type IV secretion system Intracellular growth Vesicle trafficking |
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