Dual function of a bacterial protein as an adhesin and extracellular effector of host GTPase signaling

Bacterial pathogens often target conserved cellular mechanisms within their hosts to rewire 14 signaling pathways and facilitate infection. Rho GTPases are important nodes within 15 eukaryotic signaling networks and thus constitute a common target of pathogen-mediated 16 manipulation. A diverse array of microbial mechanisms exists to interfere with Rho 17 GTPase signaling. While targeting of GTPases by secreted bacterial effectors is a well-18 known strategy bacterial pathogens employ to interfere with the host, we have recently 19 described pathogen adhesion as a novel extracellular stimulus that hijacks host GTPase 20 signaling. The Multivalent Adhesion Molecule MAM7 from Vibrio parahaemolyticus 21 directly binds host cell membrane lipids. The ensuing coalescence of phosphatidic acid 22 ligands in the host membrane leads to downstream activation of RhoA and actin 23 rearrangements. Herein, we discuss mechanistic models of lipid-mediated Rho activation 24 and the implications from the infected host’s and the pathogen’s perspective.