A phospholipase A1 antibacterial Type VI secretion effector interacts directly with the C-terminal domain of the VgrG spike protein for delivery

Mol Microbiol. 2016 Mar;99(6):1099-118. doi: 10.1111/mmi.13292. Epub 2016 Feb 10.


The Type VI secretion system (T6SS) is a multiprotein machine that delivers protein effectors in both prokaryotic and eukaryotic cells, allowing interbacterial competition and virulence. The mechanism of action of the T6SS requires the contraction of a sheath-like structure that propels a needle towards target cells, allowing the delivery of protein effectors. Here, we provide evidence that the entero-aggregative Escherichia coli Sci-1 T6SS is required to eliminate competitor bacteria. We further identify Tle1, a toxin effector encoded by this cluster and showed that Tle1 possesses phospholipase A1 and A2 activities required for the interbacterial competition. Self-protection of the attacker cell is secured by an outer membrane lipoprotein, Tli1, which binds Tle1 in a 1:1 stoichiometric ratio with nanomolar affinity, and inhibits its phospholipase activity. Tle1 is delivered into the periplasm of the prey cells using the VgrG1 needle spike protein as carrier. Further analyses demonstrate that the C-terminal extension domain of VgrG1, including a transthyretin-like domain, is responsible for the interaction with Tle1 and its subsequent delivery into target cells. Based on these results, we propose an additional mechanism of transport of T6SS effectors in which cognate effectors are selected by specific motifs located at the C-terminus of VgrG proteins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Proteins / metabolism
  • Bacterial Toxins / genetics
  • Bacterial Toxins / metabolism
  • Caenorhabditis elegans
  • Escherichia coli / metabolism*
  • Escherichia coli / pathogenicity
  • Models, Molecular
  • Multigene Family
  • Phospholipases A1 / chemistry
  • Phospholipases A1 / genetics
  • Phospholipases A1 / metabolism*
  • Protein Domains
  • Type VI Secretion Systems / genetics
  • Type VI Secretion Systems / metabolism*
  • Virulence


  • Bacterial Proteins
  • Bacterial Toxins
  • Type VI Secretion Systems
  • Phospholipases A1

Associated data

  • PDB/4UHV