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Title: An interbacterial NAD(P)+ glycohydrolase toxin requires elongation factor Tu for delivery to target cells

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. Lastly, 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.

Authors:
 [1];  [2];  [1];  [1];  [1];  [1];  [3];  [4];  [3];  [3];  [2];  [5]
  1. Univ. of Washington, Seattle, WA (United States)
  2. Max Planck Institute of Molecular Physiology, Dortmund (Germany)
  3. Univ. of Maryland, Baltimore, MD (United States)
  4. Brookhaven National Lab. (BNL), Upton, NY (United States)
  5. Univ. of Washington, Seattle, WA (United States); Howard Hughes Medical Institute, Seattle, WA (United States)
Publication Date:
Research Org.:
Brookhaven National Laboratory (BNL), Upton, NY (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES)
OSTI Identifier:
1340347
Report Number(s):
BNL-112066-2016-JA
Journal ID: ISSN 0092-8674
Grant/Contract Number:  
SC00112704
Resource Type:
Accepted Manuscript
Journal Name:
Cell
Additional Journal Information:
Journal Volume: 163; Journal Issue: 3; Journal ID: ISSN 0092-8674
Publisher:
Elsevier
Country of Publication:
United States
Language:
English
Subject:
36 MATERIALS SCIENCE

Citation Formats

Whitney, John C., Quentin, Dennis, Sawai, Shin, LeRoux, Michele, Harding, Brittany N., Ledvina, Hannah E., Tran, Bao Q., Robinson, Howard, Goo, Young Ah, Goodlett, David R., Raunser, Stefan, and Mougous, Joseph D. An interbacterial NAD(P)+ glycohydrolase toxin requires elongation factor Tu for delivery to target cells. United States: N. p., 2015. Web. doi:10.1016/j.cell.2015.09.027.
Whitney, John C., Quentin, Dennis, Sawai, Shin, LeRoux, Michele, Harding, Brittany N., Ledvina, Hannah E., Tran, Bao Q., Robinson, Howard, Goo, Young Ah, Goodlett, David R., Raunser, Stefan, & Mougous, Joseph D. An interbacterial NAD(P)+ glycohydrolase toxin requires elongation factor Tu for delivery to target cells. United States. https://doi.org/10.1016/j.cell.2015.09.027
Whitney, John C., Quentin, Dennis, Sawai, Shin, LeRoux, Michele, Harding, Brittany N., Ledvina, Hannah E., Tran, Bao Q., Robinson, Howard, Goo, Young Ah, Goodlett, David R., Raunser, Stefan, and Mougous, Joseph D. Thu . "An interbacterial NAD(P)+ glycohydrolase toxin requires elongation factor Tu for delivery to target cells". United States. https://doi.org/10.1016/j.cell.2015.09.027. https://www.osti.gov/servlets/purl/1340347.
@article{osti_1340347,
title = {An interbacterial NAD(P)+ glycohydrolase toxin requires elongation factor Tu for delivery to target cells},
author = {Whitney, John C. and Quentin, Dennis and Sawai, Shin and LeRoux, Michele and Harding, Brittany N. and Ledvina, Hannah E. and Tran, Bao Q. and Robinson, Howard and Goo, Young Ah and Goodlett, David R. and Raunser, Stefan and Mougous, Joseph D.},
abstractNote = {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. Lastly, 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.},
doi = {10.1016/j.cell.2015.09.027},
journal = {Cell},
number = 3,
volume = 163,
place = {United States},
year = {Thu Oct 08 00:00:00 EDT 2015},
month = {Thu Oct 08 00:00:00 EDT 2015}
}

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journal, November 2017

  • Zepeda-Rivera, Martha A.; Saak, Christina C.; Gibbs, Karine A.
  • Journal of Bacteriology
  • DOI: 10.1101/213785

A Type VI Secretion System Trans-Kingdom Effector Is Required for the Delivery of a Novel Antibacterial Toxin in Pseudomonas aeruginosa
journal, June 2019


Influence of 6-aminonicotinamide (6AN) on Leishmania promastigotes evaluated by metabolomics: Beyond the pentose phosphate pathway
journal, October 2018

  • Almugadam, Shawgi Hago; Trentini, Alessandro; Maritati, Martina
  • Chemico-Biological Interactions, Vol. 294
  • DOI: 10.1016/j.cbi.2018.08.014

Vibrio cholerae type 6 secretion system effector trafficking in target bacterial cells
journal, August 2017

  • Ho, Brian T.; Fu, Yang; Dong, Tao G.
  • Proceedings of the National Academy of Sciences, Vol. 114, Issue 35
  • DOI: 10.1073/pnas.1711219114

Type VI secretion system MIX‐effectors carry both antibacterial and anti‐eukaryotic activities
journal, September 2017


An onboard checking mechanism ensures effector delivery of the type VI secretion system in Vibrio cholerae
journal, October 2019

  • Liang, Xiaoye; Kamal, Fatima; Pei, Tong-Tong
  • Proceedings of the National Academy of Sciences, Vol. 116, Issue 46
  • DOI: 10.1073/pnas.1914202116

Phosphorylation decelerates conformational dynamics in bacterial translation elongation factors
journal, March 2018

  • Talavera, Ariel; Hendrix, Jelle; Versées, Wim
  • Science Advances, Vol. 4, Issue 3
  • DOI: 10.1126/sciadv.aap9714

Causalities of war: The connection between type VI secretion system and microbiota
journal, January 2020

  • Allsopp, Luke P.; Bernal, Patricia; Nolan, Laura M.
  • Cellular Microbiology, Vol. 22, Issue 3
  • DOI: 10.1111/cmi.13153

The tuberculosis necrotizing toxin is an NAD+ and NADP+ glycohydrolase with distinct enzymatic properties
text, January 2019