title: Soluble NSF attachment protein receptor molecular mimicry by a Legionella pneumophila Dot/Icm effector.
abstract: Upon infection, Legionella pneumophila uses the Dot/Icm type IV secretion system to translocate effector proteins from the Legionella-containing vacuole (LCV) into the host cell cytoplasm. The effectors target a wide array of host cellular processes that aid LCV biogenesis, including the manipulation of membrane trafficking. In this study, we used a hidden Markov model screen to identify two novel, non-eukaryotic soluble NSF attachment protein receptor (SNARE) homologs: the bacterial Legionella SNARE effector A (LseA) and viral SNARE homolog A proteins. We characterized LseA as a Dot/Icm effector of L. pneumophila, which has close homology to the Qc-SNARE subfamily. The lseA gene was present in multiple sequenced L. pneumophila strains including Corby and was well distributed among L. pneumophila clinical and environmental isolates. Employing a variety of biochemical, cell biological and microbiological techniques, we found that farnesylated LseA localized to membranes associated with the Golgi complex in mammalian cells and LseA interacted with a subset of Qa-, Qb- and R-SNAREs in host cells. Our results suggested that LseA acts as a SNARE protein and has the potential to regulate or mediate membrane fusion events in Golgi-associated pathways.
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, Brisbane, Qld., Australia.
authors.forename: Nathan P
authors.initials: NP
authors.lastname: King
authors.affiliation: Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Vic., Australia.
authors.forename: Patrice
authors.initials: P
authors.lastname: Newton
authors.affiliation: Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Vic., Australia.
authors.forename: Ralf
authors.initials: R
authors.lastname: Schuelein
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, Brisbane, Qld., Australia.
authors.forename: Darren L
authors.initials: DL
authors.lastname: Brown
authors.affiliation: Department of Parasitology, Charles University in Prague, Czech Republic.
authors.forename: Marketa
authors.initials: M
authors.lastname: Petru
authors.affiliation: Department of Parasitology, Charles University in Prague, Czech Republic.
authors.forename: Vojtech
authors.initials: V
authors.lastname: Zarsky
authors.affiliation: Department of Parasitology, Charles University in Prague, Czech Republic.
authors.forename: Pavel
authors.initials: P
authors.lastname: Dolezal
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, Brisbane, Qld., Australia.
authors.forename: Lin
authors.initials: L
authors.lastname: Luo
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, Brisbane, Qld., Australia.
authors.forename: Andrea
authors.initials: A
authors.lastname: Bugarcic
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, Brisbane, Qld., Australia.
authors.forename: Amanda C
authors.initials: AC
authors.lastname: Stanley
authors.affiliation: Tissue Repair and Regeneration Program, Institute of Health and Biomedical Innovation, School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, Qld., Australia.
authors.forename: Rachael Z
authors.initials: RZ
authors.lastname: Murray
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, Brisbane, Qld., Australia.
authors.forename: Brett M
authors.initials: BM
authors.lastname: Collins
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, Brisbane, Qld., Australia.
authors.forename: Rohan D
authors.initials: RD
authors.lastname: Teasdale
authors.affiliation: Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Vic., Australia.
authors.forename: Elizabeth L
authors.initials: EL
authors.lastname: Hartland
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, Brisbane, Qld., Australia.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Stow
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism*; D002460:Cell Line; D004847:Epithelial Cells / Q000382:microbiology; D054884:Host-Pathogen Interactions; D006801:Humans; D016952:Legionella pneumophila / Q000502:physiology*; D008264:Macrophages / Q000382:microbiology; D051379:Mice; D018716:Molecular Mimicry; D017386:Sequence Homology, Amino Acid; D052067:Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins / Q000378:metabolism*; D037521:Virulence Factors / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D052067:Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins; D037521:Virulence Factors