The protein kinase LegK2 is a T4SS effector involved in endoplasmic reticulum recruitment and intracellular replication of Legionella pneumophila

ABSTRACT

Legionella pneumophila is the aetiological agent of Legionnaire's Disease. Key of the pathogenesis of this intracellular pathogen is its ability to subvert host cell defenses, permitting intracellular replication in specialized vacuole 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. Here, in silico analysis and in vitro phosphorylation assays identified 5 functional protein kinases LegK1-LegK5 encoded by the epidemic L. pneumophila Lens strain. Except LegK5, the Legionella protein kinases are T4SS effectors. LegK2 plays a key role in bacterial virulence, as demonstrated by gene inactivation. The legK2 mutant containing vacuoles display 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.