An effector of phosphatidylinositol 3-kinase activity promotes <i>Rickettsia rickettsii</i> virulence by enhancing autophagy

The phosphatidylinositol derivative PI3P is a key second messenger that regulates multiple cellular processes, particularly membrane trafficking and autophagy. We report here that PikA, a T4SS substrate of <i>R. rickettsii</i>, functions as a PI-3 kinase that catalyzes the production of PI3P to promote autophagy influx. PikA achieves this by recruiting Beclin 1 through direct protein-protein interactions. The expression of the dual-specific PI phosphatase Myotubularin counteracted the effects of PikA and inhibited intracellular <i>R</i>. <i>rickettsii</i> replication. Our results reveal that the modulation of PI metabolism by a bacterial PI-3 kinase is critical for <i>R</i>. <i>rickettsii</i> virulence, and this pathway may provide potential target for the development of therapeutics against infections caused by this pathogen.