Research Summary

Building a network of Arf-like GTPases and their effectors in phagosome maturation

Intracellular pathogens have evolved several mechanisms to manipulate the host cellular pathways for their survival. Salmonella is one such successful pathogen that invades primarily epithelial cells and macrophages and builds its replicative niche within these cells. Most of the Salmonella effectors that it secretes in the host cytosol, and their intracellular targets are not characterized yet. Recent studies have identified Arl GTPases as important regulators of vesicular trafficking whose function is not explored during Salmonella pathogenesis. Here, we aim to understand the role of this important family of endocytic regulators in Salmonella infection. These studies will be relevant in further characterizing Salmonella phagosomes and identifying novel targets for controlling Salmonella infection. We will also address the role of lysosomal localized Arl8b that was recently shown to regulate formation of Salmonella-induced filaments (SIFs). As part of this proposal, we want to understand the mechanism by which Arl8b and its effectors regulate SIF formation. Furthermore, we aim to explore whether the crosstalk of Arls with Rabs is important during progression of Salmonella infection. We expect that results from these studies will identify unknown targets of Salmonella effectors, and will provide a better understanding of how Salmonella survives inside the host cells.                                                                        

                                   

Figure Legend: This schematic depicts the intracellular localization and associated vesicle transport pathway(s) of several Rab and Arl GTPases. Intracellular pathogens such as Salmonella modulate the function of the GTPases and their effectors to form a replicative compartment inside the host cell. SIFs: Salmonella-induced filaments; EE/SE: early endosome/sorting endosome; ERC: endocytic recycling compartment; LE: late endosome; LYS: lysosome and TGN: trans-golgi network.