David Ojcius, Philippe Verbeke, Toni Darville, Georg Häcker and colleagues show that
Chlamydia trachomatis
co-opts the PI3K pathway to prevent host-cell apoptosis. C. trachomatis replicates in an intracellular vacuole, known as an inclusion, and inhibits host-cell death in part by promoting the degradation of pro-apoptotic BH3-only proteins such as BAD. By analysing C. trachomatis-infected epithelial cells in the presence or absence of functional PI3K, Ojcius and colleagues revealed that functional PI3K protects C. trachomatis-infected cells from apoptosis. Activation of PI3K results in the phosphorylation and activation of the pro-survival protein AKT, which phosphorylates BAD. Phosphorylated BAD is retained at the Chlamydia inclusion by binding to the 14-3-3 cellular adaptor protein, which itself binds to the chlamydial inclusion protein IncG. By sequestering pro-apoptotic BAD away from the mitochondria, untimely apoptosis of the host cell is prevented.
The interaction of
Legionella pneumophila
with phosphatidylinositol lipids was investigated by Hubert Hilbi and colleagues using a
Dictyostelium discoideum
model of L. pneumophila infection. L. pneumophila replicates within a membrane-bound compartment, the Legionella-containing vacuole (LCV), which is formed by fusion with endoplasmic-reticulum-derived secretory vesicles and evolves from a 'tight vacuole' into a 'spacious vacuole'. The formation of the LCV requires the intracellular multiplication/defective organelle trafficking (Icm/Dot) type IV secretion system. The authors showed that functional PI3Ks restrict intracellular growth of L. pneumophila and promote the transition of the LCV into a spacious vacuole, implicating the PI3K pathway in the trafficking and evolution of the LCV. SidC, a protein secreted by Icm/Dot, is found on the LCV and interacts in vitro with phosphatidylinositol(4) phosphate (PI(4)P), a PI3K substrate that is found in the trans-Golgi apparatus and on the LCV membrane.
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