An Interbacterial NAD(P)+ Glycohydrolase Toxin Requires Elongation Factor Tu for Delivery to Target Cells

John C. Whitney, Dennis Quentin, Shin Sawai, Michele LeRoux, Brittany N. Harding, Hannah E. Ledvina, Bao Q. Tran, Howard Robinson, Young Ah Goo, David R. Goodlett, Stefan Raunser, Joseph D. Mougous*

*Corresponding author for this work

Research output: Contribution to journalArticle

87 Scopus citations

Abstract

Summary Type VI secretion (T6S) influences the composition of microbial communities by catalyzing the delivery of toxins between adjacent bacterial cells. Here, we demonstrate that a T6S integral membrane toxin from Pseudomonas aeruginosa, Tse6, acts on target cells by degrading the universally essential dinucleotides NAD+ and NADP+. Structural analyses of Tse6 show that it resembles mono-ADP-ribosyltransferase proteins, such as diphtheria toxin, with the exception of a unique loop that both excludes proteinaceous ADP-ribose acceptors and contributes to hydrolysis. We find that entry of Tse6 into target cells requires its binding to an essential housekeeping protein, translation elongation factor Tu (EF-Tu). These proteins participate in a larger assembly that additionally directs toxin export and provides chaperone activity. Visualization of this complex by electron microscopy defines the architecture of a toxin-loaded T6S apparatus and provides mechanistic insight into intercellular membrane protein delivery between bacteria.

Original languageEnglish (US)
Pages (from-to)607-619
Number of pages13
JournalCell
Volume163
Issue number3
DOIs
StatePublished - Oct 22 2015

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Whitney, J. C., Quentin, D., Sawai, S., LeRoux, M., Harding, B. N., Ledvina, H. E., Tran, B. Q., Robinson, H., Goo, Y. A., Goodlett, D. R., Raunser, S., & Mougous, J. D. (2015). An Interbacterial NAD(P)+ Glycohydrolase Toxin Requires Elongation Factor Tu for Delivery to Target Cells. Cell, 163(3), 607-619. https://doi.org/10.1016/j.cell.2015.09.027