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 PltA and PltB, which are encoded in the same pathogenicity islet as cdtB, associate with CdtB to form a multipartite toxin. PltA and PltB are homologs of components of the pertussis toxin, including its ADP-ribosyl transferase subunit. We also show that PltA and PltB 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.
Spanò
Stefania
S
Section of Microbial Pathogenesis, Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, CT 06536, USA.
Ugalde
Juan E
JE
Galán
Jorge E
JE
D001427:Bacterial Toxins / Q000235:genetics / Q000378:metabolism / Q000633:toxicity; D002460:Cell Line; D005098:Exotoxins / Q000235:genetics / Q000378:metabolism* / Q000633:toxicity; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D007422:Intestines / Q000166:cytology / Q000382:microbiology; D010588:Phagosomes; D012485:Salmonella typhi / Q000235:genetics / Q000472:pathogenicity*; D014617:Vacuoles; D014774:Virulence
D001427:Bacterial Toxins; D005098:Exotoxins; C067044:cytolethal distending toxin