Microb6

P. aeruginosa (Pa) can invade non-phagocytic cells. We showed that the VgrG2b effector is delivered by the T6SS machinery into the host cells where it targets the gamma-TuRC responsible for microtubule (MT) nucleation and formation. This interaction precedes a MT-dependent internalization of Pa. We propose to investigate (i) how Pa subverts the MT network to invade epithelial cells by studying MT remodeling and MT-motor recruitment upon infection (ii) interactants and function of the VgrG2b effector domain on its host targets (iii) the ultrastructure of VgrG2b which belongs to the T6SS puncturing device in plus of being an effector. We will use a combination of molecular and cellular (micro)biology, biochemical and microscopic approaches thanks to the expertise of the 2 teams on bacterial secretion systems & effectors (Partner 1), and on MT organization (Partner 2), and a collaboration for cryo-electron microscopy. Understanding pathogenic mechanisms is key for developing new antibacterial compounds.