title: A phospholipase A1 antibacterial Type VI secretion effector interacts directly with the C-terminal domain of the VgrG spike protein for delivery.
abstract: The Type VI secretion system (T6SS) is a multiprotein machine that delivers protein effectors in both prokaryotic and eukaryotic cells, allowing interbacterial competition and virulence. The mechanism of action of the T6SS requires the contraction of a sheath-like structure that propels a needle towards target cells, allowing the delivery of protein effectors. Here, we provide evidence that the entero-aggregative Escherichia coli Sci-1 T6SS is required to eliminate competitor bacteria. We further identify Tle1, a toxin effector encoded by this cluster and showed that Tle1 possesses phospholipase A1 and A2 activities required for the interbacterial competition. Self-protection of the attacker cell is secured by an outer membrane lipoprotein, Tli1, which binds Tle1 in a 1:1 stoichiometric ratio with nanomolar affinity, and inhibits its phospholipase activity. Tle1 is delivered into the periplasm of the prey cells using the VgrG1 needle spike protein as carrier. Further analyses demonstrate that the C-terminal extension domain of VgrG1, including a transthyretin-like domain, is responsible for the interaction with Tle1 and its subsequent delivery into target cells. Based on these results, we propose an additional mechanism of transport of T6SS effectors in which cognate effectors are selected by specific motifs located at the C-terminus of VgrG proteins.
authors.affiliation: Laboratoire d'Ingénierie des Systèmes Macromoléculaires, CNRS - Aix-Marseille Université, UMR 7255, Institut de Microbiologie de la Méditerranée, 31 Chemin Joseph Aiguier, 13402 Marseille Cedex 20, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Flaugnatti
authors.affiliation: Architecture et Fonction des Macromolécules Biologiques, CNRS - UMR 7257, Campus de Luminy, Case 932, 13288 Marseille Cedex 09, France.|Architecture et Fonction des Macromolécules Biologiques, Aix-Marseille Université, Campus de Luminy, Case 932, 13288 Marseille Cedex 09, France.
authors.forename: Thi Thu Hang
authors.initials: TT
authors.lastname: Le
authors.affiliation: Laboratoire d'Enzymologie Interfaciale et de Physiologie de la Lipolyse, CNRS - Aix-Marseille Université, UMR 7282, 31 Chemin Joseph Aiguier, 13402 Marseille Cedex 20, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Canaan
authors.affiliation: Laboratoire d'Ingénierie des Systèmes Macromoléculaires, CNRS - Aix-Marseille Université, UMR 7255, Institut de Microbiologie de la Méditerranée, 31 Chemin Joseph Aiguier, 13402 Marseille Cedex 20, France.
authors.forename: Marie-Stéphanie
authors.initials: MS
authors.lastname: Aschtgen
authors.affiliation: Architecture et Fonction des Macromolécules Biologiques, CNRS - UMR 7257, Campus de Luminy, Case 932, 13288 Marseille Cedex 09, France.|Architecture et Fonction des Macromolécules Biologiques, Aix-Marseille Université, Campus de Luminy, Case 932, 13288 Marseille Cedex 09, France.
authors.forename: Van Son
authors.initials: VS
authors.lastname: Nguyen
authors.affiliation: Architecture et Fonction des Macromolécules Biologiques, CNRS - UMR 7257, Campus de Luminy, Case 932, 13288 Marseille Cedex 09, France.|Architecture et Fonction des Macromolécules Biologiques, Aix-Marseille Université, Campus de Luminy, Case 932, 13288 Marseille Cedex 09, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Blangy
authors.affiliation: Architecture et Fonction des Macromolécules Biologiques, CNRS - UMR 7257, Campus de Luminy, Case 932, 13288 Marseille Cedex 09, France.|Architecture et Fonction des Macromolécules Biologiques, Aix-Marseille Université, Campus de Luminy, Case 932, 13288 Marseille Cedex 09, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Kellenberger
authors.affiliation: Architecture et Fonction des Macromolécules Biologiques, CNRS - UMR 7257, Campus de Luminy, Case 932, 13288 Marseille Cedex 09, France.|Architecture et Fonction des Macromolécules Biologiques, Aix-Marseille Université, Campus de Luminy, Case 932, 13288 Marseille Cedex 09, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Roussel
authors.affiliation: Architecture et Fonction des Macromolécules Biologiques, CNRS - UMR 7257, Campus de Luminy, Case 932, 13288 Marseille Cedex 09, France.|Architecture et Fonction des Macromolécules Biologiques, Aix-Marseille Université, Campus de Luminy, Case 932, 13288 Marseille Cedex 09, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Cambillau
authors.affiliation: Laboratoire d'Ingénierie des Systèmes Macromoléculaires, CNRS - Aix-Marseille Université, UMR 7255, Institut de Microbiologie de la Méditerranée, 31 Chemin Joseph Aiguier, 13402 Marseille Cedex 20, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Cascales
authors.affiliation: Laboratoire d'Ingénierie des Systèmes Macromoléculaires, CNRS - Aix-Marseille Université, UMR 7255, Institut de Microbiologie de la Méditerranée, 31 Chemin Joseph Aiguier, 13402 Marseille Cedex 20, France.
authors.forename: Laure
authors.initials: L
authors.lastname: Journet
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism; D001427:Bacterial Toxins / Q000235:genetics / Q000378:metabolism; D017173:Caenorhabditis elegans; D004926:Escherichia coli / Q000378:metabolism* / Q000472:pathogenicity; D008958:Models, Molecular; D005810:Multigene Family; D054466:Phospholipases A1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000072417:Protein Domains; D000069376:Type VI Secretion Systems / Q000235:genetics / Q000378:metabolism*; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D001427:Bacterial Toxins; D000069376:Type VI Secretion Systems; D054466:Phospholipases A1