title: Functional type 1 secretion system involved in Legionella pneumophila virulence.
abstract: Legionella pneumophila is a Gram-negative pathogen found mainly in water, either in a free-living form or within infected protozoans, where it replicates. This bacterium can also infect humans by inhalation of contaminated aerosols, causing a severe form of pneumonia called legionellosis or Legionnaires' disease. The involvement of type II and IV secretion systems in the virulence of L. pneumophila is now well documented. Despite bioinformatic studies showing that a type I secretion system (T1SS) could be present in this pathogen, the functionality of this system based on the LssB, LssD, and TolC proteins has never been established. Here, we report the demonstration of the functionality of the T1SS, as well as its role in the infectious cycle of L. pneumophila. Using deletion mutants and fusion proteins, we demonstrated that the repeats-in-toxin protein RtxA is secreted through an LssB-LssD-TolC-dependent mechanism. Moreover, fluorescence monitoring and confocal microscopy showed that this T1SS is required for entry into the host cell, although it seems dispensable to the intracellular cycle. Together, these results underline the active participation of L. pneumophila, via its T1SS, in its internalization into host cells.
authors.affiliation: CIRI, International Center for Infectiology Research, Legionella Pathogenesis Group, Université de Lyon, Lyon, France Inserm, U1111, Lyon, France Ecole Normale Supérieure de Lyon, Lyon, France Université Lyon 1, Centre International de Recherche en Infectiologie, Lyon, France CNRS, UMR5308, Lyon, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Fuche
authors.affiliation: CIRI, International Center for Infectiology Research, Legionella Pathogenesis Group, Université de Lyon, Lyon, France Inserm, U1111, Lyon, France Ecole Normale Supérieure de Lyon, Lyon, France Université Lyon 1, Centre International de Recherche en Infectiologie, Lyon, France CNRS, UMR5308, Lyon, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Vianney
authors.affiliation: CIRI, International Center for Infectiology Research, Legionella Pathogenesis Group, Université de Lyon, Lyon, France Inserm, U1111, Lyon, France Ecole Normale Supérieure de Lyon, Lyon, France Université Lyon 1, Centre International de Recherche en Infectiologie, Lyon, France CNRS, UMR5308, Lyon, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Andrea
authors.affiliation: CIRI, International Center for Infectiology Research, Legionella Pathogenesis Group, Université de Lyon, Lyon, France Inserm, U1111, Lyon, France Ecole Normale Supérieure de Lyon, Lyon, France Université Lyon 1, Centre International de Recherche en Infectiologie, Lyon, France CNRS, UMR5308, Lyon, France.
authors.forename: Patricia
authors.initials: P
authors.lastname: Doublet
authors.affiliation: CIRI, International Center for Infectiology Research, Legionella Pathogenesis Group, Université de Lyon, Lyon, France Inserm, U1111, Lyon, France Ecole Normale Supérieure de Lyon, Lyon, France Université Lyon 1, Centre International de Recherche en Infectiologie, Lyon, France CNRS, UMR5308, Lyon, France christophe.gilbert.bio@univ-lyon1.fr.
authors.forename: Christophe
authors.initials: C
authors.lastname: Gilbert
mesh_terms: D058947:Bacterial Secretion Systems; D004705:Endocytosis; D055786:Gene Knockout Techniques; D006801:Humans; D016952:Legionella pneumophila / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009000:Monocytes / Q000382:microbiology; D020298:U937 Cells; D014774:Virulence; D037521:Virulence Factors / Q000378:metabolism*
chemical_list: D058947:Bacterial Secretion Systems; D008565:Membrane Proteins; D037521:Virulence Factors