Host adaptation of a bacterial toxin from the human pathogen salmonella typhi

Lingquan Deng, Jeongmin Song, Xiang Gao, Jiawei Wang, Hai Yu, Xi Chen, Nissi Varki, Yuko Naito-Matsui, Jorge E. Galán, Ajit Varki

Research output: Contribution to journalArticle

50 Scopus citations

Abstract

Salmonella Typhi is an exclusive human pathogen that causes typhoid fever. Typhoid toxin is a S. Typhi virulence factor that can reproduce most of the typhoid fever symptoms in experimental animals. Toxicity depends on toxin binding to terminally sialylated glycans on surface glycoproteins. Human glycans are unusual because of the lack of CMAH, which in other mammals converts N-acetylneuraminic acid (Neu5Ac) to N-glycolylneuraminic acid (Neu5Gc). Here, we report that typhoid toxin binds to and is toxic toward cells expressing glycans terminated in Neu5Ac (expressed by humans) over glycans terminated in Neu5Gc (expressed by other mammals). Mice constitutively expressing CMAH thus displaying Neu5Gc in all tissues are resistant to typhoid toxin. The atomic structure of typhoid toxin bound to Neu5Ac reveals the structural bases for its binding specificity. These findings provide insight into the molecular bases for Salmonella Typhi's host specificity and may help the development of therapies for typhoid fever.

Original languageEnglish (US)
Pages (from-to)1290-1299
Number of pages10
JournalCell
Volume159
Issue number6
DOIs
StatePublished - Dec 4 2014

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Deng, L., Song, J., Gao, X., Wang, J., Yu, H., Chen, X., Varki, N., Naito-Matsui, Y., Galán, J. E., & Varki, A. (2014). Host adaptation of a bacterial toxin from the human pathogen salmonella typhi. Cell, 159(6), 1290-1299. https://doi.org/10.1016/j.cell.2014.10.057