Programmed Secretion Arrest and Receptor-Triggered Toxin Export during Antibacterial Contact-Dependent Growth Inhibition

• Published in: Cell Vol. 175; no. 4; pp. 921 - 933.e14
• Main Authors: Ruhe, Zachary C., Subramanian, Poorna, Song, Kiho, Nguyen, Josephine Y., Stevens, Taylor A., Low, David A., Jensen, Grant J., Hayes, Christopher S.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2018
• Subjects: Antibiosis; bacterial competition; BamA; Cell Surface Extensions - metabolism; Cell Surface Extensions - ultrastructure; Escherichia coli - metabolism; Escherichia coli Proteins - chemistry; Escherichia coli Proteins - metabolism; Membrane Proteins - chemistry; Membrane Proteins - metabolism; outer membrane; Protein Domains; Receptors, Cell Surface - metabolism; self-nonself discrimination; toxin-immunity proteins; Tsx; two-partner secretion; type V secretion system; Type V Secretion Systems - metabolism; β-barrel protein; outer membrane; two-partner secretion; self-nonself discrimination; toxin-immunity proteins; bacterial competition; Tsx; BamA; type V secretion system; β-barrel protein
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/j.cell.2018.10.033

Contact-dependent growth inhibition (CDI) entails receptor-mediated delivery of CdiA-derived toxins into Gram-negative target bacteria. Using electron cryotomography, we show that each CdiA effector protein forms a filament extending ∼33 nm from the cell surface. Remarkably, the extracellular filament represents only the N-terminal half of the effector. A programmed secretion arrest sequesters the C-terminal half of CdiA, including the toxin domain, in the periplasm prior to target-cell recognition. Upon binding receptor, CdiA secretion resumes, and the periplasmic FHA-2 domain is transferred to the target-cell outer membrane. The C-terminal toxin region of CdiA then penetrates into the target-cell periplasm, where it is cleaved for subsequent translocation into the cytoplasm. Our findings suggest that the FHA-2 domain assembles into a transmembrane conduit for toxin transport into the periplasm of target bacteria. We propose that receptor-triggered secretion ensures that FHA-2 export is closely coordinated with integration into the target-cell outer membrane. [Display omitted] [Display omitted] •CdiA forms a filament, extending ∼33 nm from the cell surface•CdiA export is arrested, and its C-terminal toxin domain remains in the periplasm•CdiA secretion resumes upon binding to specific receptors on target bacteria•The FHA-2 domain interacts stably with target cells and may form a toxin translocon Insights into the architecture and function of bacterial contact-dependent inhibition systems reveal a stalled, partially secreted state that ensures toxin export only upon target cell engagement.