Diverse type VI secretion phospholipases are functionally plastic antibacterial effectors

Nature. 2013 Apr 25;496(7446):508-12. doi: 10.1038/nature12074. Epub 2013 Apr 3.


Membranes allow the compartmentalization of biochemical processes and are therefore fundamental to life. The conservation of the cellular membrane, combined with its accessibility to secreted proteins, has made it a common target of factors mediating antagonistic interactions between diverse organisms. Here we report the discovery of a diverse superfamily of bacterial phospholipase enzymes. Within this superfamily, we defined enzymes with phospholipase A1 and A2 activity, which are common in host-cell-targeting bacterial toxins and the venoms of certain insects and reptiles. However, we find that the fundamental role of the superfamily is to mediate antagonistic bacterial interactions as effectors of the type VI secretion system (T6SS) translocation apparatus; accordingly, we name these proteins type VI lipase effectors. Our analyses indicate that PldA of Pseudomonas aeruginosa, a eukaryotic-like phospholipase D, is a member of the type VI lipase effector superfamily and the founding substrate of the haemolysin co-regulated protein secretion island II T6SS (H2-T6SS). Although previous studies have specifically implicated PldA and the H2-T6SS in pathogenesis, we uncovered a specific role for the effector and its secretory machinery in intra- and interspecies bacterial interactions. Furthermore, we find that this effector achieves its antibacterial activity by degrading phosphatidylethanolamine, the major component of bacterial membranes. The surprising finding that virulence-associated phospholipases can serve as specific antibacterial effectors suggests that interbacterial interactions are a relevant factor driving the continuing evolution of pathogenesis.

Publication types

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

MeSH terms

  • Anti-Bacterial Agents / metabolism*
  • Antibiosis*
  • Bacterial Secretion Systems*
  • Cell Membrane / chemistry
  • Cell Membrane / metabolism
  • Evolution, Molecular
  • Phosphatidylethanolamines / metabolism
  • Phospholipase D / chemistry
  • Phospholipase D / classification
  • Phospholipase D / metabolism*
  • Phylogeny
  • Pseudomonas aeruginosa / enzymology*
  • Pseudomonas aeruginosa / metabolism
  • Pseudomonas aeruginosa / pathogenicity
  • Species Specificity
  • Substrate Specificity
  • Virulence Factors / chemistry
  • Virulence Factors / metabolism


  • Anti-Bacterial Agents
  • Bacterial Secretion Systems
  • Phosphatidylethanolamines
  • Virulence Factors
  • phosphatidylethanolamine
  • Phospholipase D