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Cell Host Microbe. 2016 Nov 9;20(5):682-689. doi: 10.1016/j.chom.2016.10.005.

Receptor-Mediated Sorting of Typhoid Toxin during Its Export from Salmonella Typhi-Infected Cells.

Author information

1
Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06536, USA.
2
Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06536, USA. Electronic address: jorge.galan@yale.edu.

Abstract

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.

KEYWORDS:

Salmonella Typhi pathogenesis; bacterial pathogenesis; bacterial toxins; host-pathogen interactions; sialoglycans; vesicle traffic

PMID:
27832592
PMCID:
PMC5110213
DOI:
10.1016/j.chom.2016.10.005
[Indexed for MEDLINE]
Free PMC Article

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