title: Protein kinase LegK2 is a type IV secretion system effector involved in endoplasmic reticulum recruitment and intracellular replication of Legionella pneumophila.
abstract: Legionella pneumophila is the etiological agent of Legionnaires' disease. Crucial to the pathogenesis of this intracellular pathogen is its ability to subvert host cell defenses, permitting intracellular replication in specialized vacuoles within host cells. The Dot/Icm type IV secretion system (T4SS), which translocates a large number of bacterial effectors into host cell, is absolutely required for rerouting the Legionella phagosome. Many Legionella effectors display distinctive eukaryotic domains, among which are protein kinase domains. In silico analysis and in vitro phosphorylation assays identified five functional protein kinases, LegK1 to LegK5, encoded by the epidemic L. pneumophila Lens strain. Except for LegK5, the Legionella protein kinases are all T4SS effectors. LegK2 plays a key role in bacterial virulence, as demonstrated by gene inactivation. The legK2 mutant containing vacuoles displays less-efficient recruitment of endoplasmic reticulum markers, which results in delayed intracellular replication. Considering that a kinase-dead substitution mutant of legK2 exhibits the same virulence defects, we highlight here a new molecular mechanism, namely, protein phosphorylation, developed by L. pneumophila to establish a replicative niche and evade host cell defenses.
authors.affiliation: Université de Lyon, Université Lyon 1, CNRS UMR 5240 Microbiologie, Adaptation et Pathogénie, 69622 Villeurbanne, France.
authors.forename: Eva
authors.initials: E
authors.lastname: Hervet
authors.forename: Xavier
authors.initials: X
authors.lastname: Charpentier
authors.forename: Anne
authors.initials: A
authors.lastname: Vianney
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Lazzaroni
authors.forename: Christophe
authors.initials: C
authors.lastname: Gilbert
authors.forename: Danièle
authors.initials: D
authors.lastname: Atlan
authors.forename: Patricia
authors.initials: P
authors.lastname: Doublet
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D058947:Bacterial Secretion Systems / Q000235:genetics*; D004721:Endoplasmic Reticulum / Q000201:enzymology; D042541:Intracellular Space / Q000201:enzymology; D016952:Legionella pneumophila / Q000201:enzymology / Q000235:genetics* / Q000472:pathogenicity*; D051379:Mice; D008969:Molecular Sequence Data; D011494:Protein Kinases / Q000235:genetics* / Q000378:metabolism; D016415:Sequence Alignment; D014774:Virulence
chemical_list: D058947:Bacterial Secretion Systems; D011494:Protein Kinases