Delivery of a Salmonella typhi exotoxin from a host intracellular compartment

Salmonella Typhi, an exclusive human pathogen and the cause of typhoid fever, expresses a functional cytolethal distending toxin for which only the active subunit, CdtB, has been identified. Here, we show that PItA and PItB, which are encoded in the same pathogenicity islet as cdtB, associate with CdtB to form a multipartite toxin. PItA and PItB are homologs of components of the pertussis toxin, including its ADP-ribosyl transferase subunit. We also show that PItA and PItB are required for the delivery of CdtB from an intracellular compartment to target cells via autocrine and paracrine pathways. We hypothesize that this toxin, which we have named typhoid toxin, and its delivery mechanism may contribute to S. Typhi's unique virulence properties.