Pathogen effector protein screening in yeast identifies Legionella factors that interfere with membrane trafficking

Genome Dynamics in Legionella: The Basis of Versatility and Adaptation to Intracellular Replication

“…The main secretion system of Legionella, essential for intracellular growth, is the type IVB Dot/Icm secretion system (Marra and Shuman 1992;Berger and Isberg 1993). Using many dif-ferent methods it has been shown that at least 275 L. pneumophila proteins are secreted by this system (Campodonico et al 2005;de Felipe et al 2005;Shohdy et al 2005;de Felipe et al 2008;Burstein et al 2009;Heidtman et al 2009;Zhu et al 2011), which represents nearly 10% of the protein-coding genes predicted in the L. pneumophila genomes. At least 75 of these are eukaryotic-like proteins or carry eukaryotic domains and, for certain of these, it has also been shown experimentally that they interfere with host-cell signaling pathways ( Table 2).…”

A Legionella pneumophila -translocated substrate that is required for growth within macrophages and protection from host cell death

“…In the absence of the Dot/Icm system, the bacteria are targeted into the endocytic path and fail to replicate intracellularly (7). A large number of proteins have been identified that are translocated across the LCV membrane by the Dot/Icm system, including several that seem to manipulate vesicle traffic between the endoplasmic reticulum and the Golgi apparatus (15)(16)(17). Mutations eliminating production of many of these substrates have been isolated, but they have little or no effect on intracellular growth, probably because of functional redundancy (17).…”

Structural basis for the recruitment and activation of the Legionella phospholipase VipD by the host GTPase Rab5

“…VipD was originally identified in a screen for L. pneumophila effectors that interfere with the vacuolar sorting pathway in yeast (11). The N-terminal half of VipD possesses high homology to patatin, a lipid acyl hydrolase present in the potato tuber (12,13).…”

“…VipD is a T4SS-translocated substrate of Legionella pneumophila, the causative agent of a potentially fatal pneumonia known as Legionnaires' disease, and another example of an effector whose catalytic activity depends on the presence of a host factor (11)(12)(13)(14). Following uptake by human alveolar macrophages, L. pneumophila translocates VipD together with more than 250 other effector proteins through its Dot/Icm T4SS into the host cell cytoplasm (15).…”