Legionella Effector RavD Binds Host Phosphoinositide‐3‐phosphate and Contributes to Lysosomal Avoidance

Abstract

Subversion of phosphoinositide lipids is a key strategy that bacterial pathogens employ to survive within hosts. Due to the importance of phosphoinositides in phagocytosis, bacterial pathogens that infect innate immune cells manipulate these lipids to alter phagosome maturation with the purpose of converting the nascent phagosome into a replication‐permissive niche. The intracellular bacterial pathogen, Legionella pneumophila, the causative agent of a severe pneumonia known as Legionnaires' disease, infects alveolar macrophages where it proliferates within the safety of a vacuole. Upon phagocytosis, L. pneumophila hijacks the nascent phagosome and remodels the cytosolic façade of the phagosomal membrane by stimulating fusion with vesicles derived from the endoplasmic reticulum. This process relies on the function of bacterial effector proteins translocated directly into the host cell via a specialized secretion system. A number of L. pneumophila effector proteins have been shown to bind phosphoinositides either for the purpose of manipulating their metabolism or as a means of targeting specific host membrane compartments. Our preliminary data indicate that many more phosphoinositide‐binding effectors remain to be discovered. Here, we show that the L. pneumophila effector, RavD, is a novel phosphoinositide‐3‐phosphate (PI3P) binding‐protein. We establish that RavD is found on the Legionella‐containing vacuole (LCV) at early stages of infection and harbors its PI3P binding domain within the C terminal region of the protein. In the absence of the ravD gene, the LCV accumulates lysosomal markers at 2 hours post‐infection, consistent with the notion that RavD function is necessary to arrest phagosome maturation.Support or Funding InformationThis work was supported by the University of Delaware Research Foundation.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.