title: Dual function of a bacterial protein as an adhesin and extracellular effector of host GTPase signaling.
abstract: Bacterial pathogens often target conserved cellular mechanisms within their hosts to rewire signaling pathways and facilitate infection. Rho GTPases are important nodes within eukaryotic signaling networks and thus constitute a common target of pathogen-mediated manipulation. A diverse array of microbial mechanisms exists to interfere with Rho GTPase signaling. While targeting of GTPases by secreted bacterial effectors is a well-known strategy bacterial pathogens employ to interfere with the host, we have recently described pathogen adhesion as a novel extracellular stimulus that hijacks host GTPase signaling. The Multivalent Adhesion Molecule MAM7 from Vibrio parahaemolyticus directly binds host cell membrane lipids. The ensuing coalescence of phosphatidic acid ligands in the host membrane leads to downstream activation of RhoA and actin rearrangements. Herein, we discuss mechanistic models of lipid-mediated Rho activation and the implications from the infected host's and the pathogen's perspective.
authors.affiliation: a Institute of Microbiology and Infection ; School of Biosciences ; University of Birmingham ; Edgbaston, Birmingham , United Kingdom.
authors.forename: Daniel Henry
authors.initials: DH
authors.lastname: Stones
authors.forename: Anne Marie
authors.initials: AM
authors.lastname: Krachler
mesh_terms: D000199:Actins / Q000378:metabolism; D018829:Adhesins, Bacterial / Q000378:metabolism; D001426:Bacterial Proteins / Q000378:metabolism*; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D006801:Humans; D008563:Membrane Lipids / Q000378:metabolism; D015398:Signal Transduction; D014735:Vibrio Infections / Q000378:metabolism* / Q000382:microbiology; D014736:Vibrio parahaemolyticus / Q000378:metabolism / Q000472:pathogenicity*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D000199:Actins; D018829:Adhesins, Bacterial; D001426:Bacterial Proteins; D008563:Membrane Lipids; C066737:RHOA protein, human; D020558:GTP Phosphohydrolases; D020742:rhoA GTP-Binding Protein
keywords: Rho GTPases; RhoA; Vibrio; actin dynamics; adhesin; effector; host-pathogen interaction; lipid signaling; phosphatidic acid