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Salmonella is a facultative intracellular pathogen that invades epithelial cells of the intestine using the SPI‐1 Type 3 secretion System (T3SS). Insertion of the SPI‐1 T3SS translocon is facilitated by acylation of the translocator SipB, which involves a protein–protein interaction with the acyl carrier protein IacP. Using nuclear magnetic resonance and biological tests, we identified the residues of IacP that are involved in the interaction with SipB. Our results suggest that the 4′‐phosphopantetheine group that functionalizes IacP participates in the interaction. Its solvent exposition may rely on two residues highly conserved in acyl carrier proteins associated with T3SS. This study is the first to address the specificity of acyl carrier proteins associated with T3SS. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]