Legionella blocks autophagy by cleaving STX17 (syntaxin 17)

Abstract

Pathogens subvert host defense systems including autophagy and apoptosis for their survival and proliferation. Legionella pneumophila is a Gram-negative bacterium that grows in alveolar macrophages and causes severe pneumonia. Early during infection Legionella secretes effector proteins that convert the plasma membrane-derived vacuole containing Legionella into an endoplasmic reticulum (ER)-like replicative vacuole. These vacuoles ultimately fuse with the ER, where the pathogen replicates. Recently, we showed that one of the effectors, Lpg1137, is a serine protease that targets the mitochondria-associated ER membrane (MAM) and degrades STX17 (syntaxin 17), a SNARE implicated in macroautophagy/autophagy as well as mitochondria dynamics and membrane trafficking in fed cells. Degradation of STX17 blocks autophagy and BAX-induced apoptosis.

Keywords: BAX; Legionella; RavZ; STX17; apoptosis; autophagy; endoplasmic reticulum; mitochondria; mitochondria-associated membrane.

Figure 1.

Lpg1137 cleaves STX17, and prevents autophagy and apoptosis. STX17 participates in mitochondrial division in fed cells, and autophagosome formation and fusion with lysosomes in starved cells. Lpg1137, which is delivered into the host cell cytosol, cleaves STX17 and thereby abrogates autophagy by preventing PtdIns3P formation at the MAM, and apoptosis by blocking the DNM1L-dependent translocation of the proapoptotic protein BAX to mitochondria.