A functionally diverse superfamily of bacterial phospholipase enzymes that mediate antagonisitc interactions as effectors of the type VI secretion system is uncovered; these enzymes degrade the bacterial membrane, representing a novel mechanism of bacterial competition. Secreted bacterial phospholipases have important roles in bacterial pathogenesis, targeting host cellular membranes and causing tissue destruction, inflammation and the disruption of intracellular trafficking pathways. Here Joseph Mougous and colleagues report the discovery of a diverse superfamily of bacterial phospholipases and show that they do more than simply target eukaryotic host cells. They also have intra- and interspecies antibacterial activity through the degradation of phosphatidylethanolamine in bacterial membranes. This work suggests that interbacterial interactions may be significant factors in the progression of infections, and indicates vulnerabilities that might yield candidate antibacterial targets. 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 reptiles1,2. 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 D3, 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 pathogenesis3,4,5, 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.

Diverse type VI secretion phospholipases are functionally plastic antibacterial effectors