Receptor-Mediated Sorting of Typhoid Toxin during Its Export from Salmonella Typhi-Infected Cells.
Typhoid toxin is an essential virulence factor of Salmonella Typhi, the cause of typhoid fever. Typhoid toxin is secreted into the lumen of Salmonella-containing vacuole (SCV), after which it is packaged into vesicle carrier intermediates and released extracellularly through incompletely understood mechanisms. Following export, the toxin targets cells by interacting with human-specific Neu5Ac-terminated glycan receptors. We show that typhoid toxin is sorted from the SCV into vesicle carrier intermediates via interactions of its B subunit, PltB, with specific lumenal sialylated glycan packaging receptors. Cells deficient in N-glycosylation or the synthesis of specific gangliosides or displaying Neu5Gc-terminated, as opposed to Neu5Ac-terminated, glycans do not support typhoid toxin export. Additionally, typhoid toxin packaging requires the specific SCV environment, as toxin produced by an S. Typhi mutant with impaired trafficking is not properly sorted into vesicles. These results reveal how the exotoxin of an intracellular pathogen engages host pathways for packaging and release.
Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06536, USA.
Shu-Jung
SJ
Chang
Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06536, USA.
Jeongmin
J
Song
Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06536, USA. Electronic address: jorge.galan@yale.edu.
Jorge E
JE
Galán
D001427:Bacterial Toxins / Q000378:metabolism*; D005732:Gangliosides / Q000378:metabolism; D006801:Humans; D011485:Protein Binding; D021122:Protein Subunits / Q000378:metabolism; D021381:Protein Transport; D012485:Salmonella typhi / Q000378:metabolism*; D022161:Transport Vesicles / Q000378:metabolism*
D001427:Bacterial Toxins; D005732:Gangliosides; D021122:Protein Subunits
Salmonella Typhi pathogenesis; bacterial pathogenesis; bacterial toxins; host-pathogen interactions; sialoglycans; vesicle traffic