title: A Legionella effector modulates host cytoskeletal structure by inhibiting actin polymerization.
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.
authors.affiliation: 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; Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, USA.
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Guo
authors.affiliation: Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Stephenson
authors.affiliation: Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, USA.
authors.forename: Jiazhang
authors.initials: J
authors.lastname: Qiu
authors.affiliation: 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.
authors.forename: Shijun
authors.initials: S
authors.lastname: Zheng
authors.affiliation: Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, USA. Electronic address: luoz@purdue.edu.
authors.forename: Zhao-Qing
authors.initials: ZQ
authors.lastname: Luo
mesh_terms: D000199:Actins / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism*; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D057809:HEK293 Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D007875:Legionella / Q000235:genetics* / Q000472:pathogenicity; D050296:Microbial Viability / Q000187:drug effects*; D010957:Plasmids / Q000235:genetics; D058105:Polymerization / Q000187:drug effects; D051304:Profilins / Q000235:genetics / Q000378:metabolism*; D015003:Yeasts / Q000187:drug effects*
chemical_list: D000199:Actins; D001426:Bacterial Proteins; D051304:Profilins
keywords: Intracellular growth; Profilin; Type IV secretion system; Vesicle trafficking