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

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 2015 Oct 13

PMID 26456113

Citations 130

Authors

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

Affiliations

Soon will be listed here.

Abstract

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.

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