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

Cell. 2015 Oct 22;163(3):607-19. doi: 10.1016/j.cell.2015.09.027. Epub 2015 Oct 8.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP Ribose Transferases / metabolism
  • Bacterial Toxins / chemistry
  • Bacterial Toxins / metabolism*
  • Models, Molecular
  • NAD / metabolism
  • NAD+ Nucleosidase / chemistry
  • NAD+ Nucleosidase / metabolism*
  • NADP / metabolism
  • Peptide Elongation Factor Tu / chemistry
  • Peptide Elongation Factor Tu / metabolism*
  • Protein Structure, Tertiary
  • Pseudomonas aeruginosa / enzymology
  • Pseudomonas aeruginosa / metabolism*
  • Type VI Secretion Systems / chemistry*
  • Type VI Secretion Systems / metabolism


  • Bacterial Toxins
  • Type VI Secretion Systems
  • NAD
  • NADP
  • ADP Ribose Transferases
  • NAD+ Nucleosidase
  • Peptide Elongation Factor Tu

Associated data

  • PDB/4ZUY
  • PDB/4ZV0
  • PDB/4ZV4