title: Acylation of the Type 3 Secretion System Translocon Using a Dedicated Acyl Carrier Protein.
abstract: Bacterial pathogens often deliver effectors into host cells using type 3 secretion systems (T3SS), the extremity of which forms a translocon that perforates the host plasma membrane. The T3SS encoded by Salmonella pathogenicity island 1 (SPI-1) is genetically associated with an acyl carrier protein, IacP, whose role has remained enigmatic. In this study, using tandem affinity purification, we identify a direct protein-protein interaction between IacP and the translocon protein SipB. We show, by mass spectrometry and radiolabelling, that SipB is acylated, which provides evidence for a modification of the translocon that has not been described before. A unique and conserved cysteine residue of SipB is identified as crucial for this modification. Although acylation of SipB was not essential to virulence, we show that this posttranslational modification promoted SipB insertion into host-cell membranes and pore-forming activity linked to the SPI-1 T3SS. Cooccurrence of acyl carrier and translocon proteins in several γ- and β-proteobacteria suggests that acylation of the translocon is conserved in these other pathogenic bacteria. These results also indicate that acyl carrier proteins, known for their involvement in metabolic pathways, have also evolved as cofactors of new bacterial protein lipidation pathways.
authors.affiliation: Aix Marseille Univ, CNRS, IMM, LISM, Marseille, France.
authors.forename: Julie P
authors.identifier: 0000-0002-9520-537X
authors.initials: JP
authors.lastname: Viala
authors.affiliation: Aix Marseille Univ, CNRS, IMM, LISM, Marseille, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Prima
authors.affiliation: Aix Marseille Univ, CNRS, IMM, Proteomic Platform- IBISA, Marseille, France.
authors.forename: Rémy
authors.initials: R
authors.lastname: Puppo
authors.affiliation: Aix Marseille Univ, CNRS, IMM, LCB, Marseille, France.
authors.forename: Rym
authors.initials: R
authors.lastname: Agrebi
authors.affiliation: Aix Marseille Univ, CNRS, IMM, LISM, Marseille, France.
authors.forename: Mickaël J
authors.initials: MJ
authors.lastname: Canestrari
authors.affiliation: Aix Marseille Univ, CNRS, IMM, Proteomic Platform- IBISA, Marseille, France.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Lignon
authors.affiliation: Aix Marseille Univ, CNRS, IMM, LISM, Marseille, France.
authors.forename: Nicolas
authors.identifier: 0000-0001-6088-3376
authors.initials: N
authors.lastname: Chauvin
authors.affiliation: Aix Marseille Univ, CNRS, INSERM, CIML, Marseille, France.
authors.forename: Stéphane
authors.identifier: 0000-0001-6578-5177
authors.initials: S
authors.lastname: Méresse
authors.affiliation: Aix Marseille Univ, CNRS, IMM, LCB, Marseille, France.
authors.forename: Tâm
authors.initials: T
authors.lastname: Mignot
authors.affiliation: Aix Marseille Univ, CNRS, IMM, Proteomic Platform- IBISA, Marseille, France.
authors.forename: Régine
authors.initials: R
authors.lastname: Lebrun
authors.affiliation: Aix Marseille Univ, CNRS, IMM, LISM, Marseille, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Bouveret
mesh_terms: D000107:Acetylation; D000213:Acyl Carrier Protein / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D012486:Salmonella typhimurium / Q000235:genetics / Q000378:metabolism; D000069296:Type III Secretion Systems / Q000378:metabolism*
chemical_list: D000213:Acyl Carrier Protein; D001426:Bacterial Proteins; D008565:Membrane Proteins; D000069296:Type III Secretion Systems; C094579:invasion protein B, Salmonella typhimurium