Delivery of Bordetella pertussis adenylate cyclase toxin to target cells via outer membrane vesicles

Bordetella pertussis adenylate cyclase toxin (ACT) intoxicates cells by producing intracellular cAMP. B. pertussis outer membrane vesicles (OMV) contain ACT on their surface (OMV–ACT), but the properties of OMV–ACT were previously unknown. We found that B. pertussis in the lung from a fatal pertussis case contains OMV, suggesting an involvement in pathogenesis. OMV–ACT and ACT intoxicate cells with and without the toxin’s receptor CD11b/CD18. Intoxication by ACT is blocked by antitoxin and anti-CD11b antibodies, but not by cytochalasin-D; in contrast, OMV–ACT is unaffected by either antibody and blocked by cytochalasin-D. Thus OMV–ACT can deliver ACT by processes distinct from those of ACT alone.

► Bordetella pertussis produce outer membrane vesicles (OMV) that contain biologically active adenylate cyclase toxin (ACT).
► OMV–ACT enter host cells by a mechanism distinct from soluble ACT.
► B. pertussis produce OMV in vivo during the course of a natural human pertussis infection.