Diverse type VI secretion phospholipases are functionally plastic antibacterial effectors.
Diverse type VI secretion phospholipases are functionally plastic antibacterial effectors.
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膜允许生物化学过程的区隔，因此是生命的基础。细胞膜的保守性，加上其对分泌蛋白的可及性，使其成为多种生物之间介导拮抗相互作用的因子的共同靶点。在这里，我们报告了细菌磷脂酶的一个不同的超家族的发现。在这个超家族中，我们定义了具有磷脂酶A1 （PLA1）和A2 （PLA2）活性的酶，它们在宿主细胞靶向细菌毒素和某些昆虫和爬行动物的毒液中很常见。然而，我们发现超家族的基本作用是作为VI型分泌系统（T6SS）易位装置的效应物介导拮抗细菌相互作用；因此，我们将这些蛋白命名为VI型脂肪酶效应器（Tle）。我们的分析表明，铜绿假单胞菌的PldA是一种真核样磷脂酶D (PLD)，是Tle超家族的成员，也是溶血素共同调节蛋白分泌岛II T6SS （H2-T6SS）的基础底物。虽然先前的研究明确指出PldA和H2-T6SS在发病机制中起作用，但我们发现了效应物及其分泌机制在种内和种间细菌相互作用中的特定作用。此外，我们发现该效应物通过降解细菌膜的主要成分磷脂酰乙醇胺（PE）来实现其抗菌活性。令人惊讶的是，毒力相关磷脂酶可以作为特定的抗菌效应物，这表明细菌间的相互作用是推动发病机制不断进化的一个相关因素。
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 (PLA1) and A2 (PLA2) 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 (Tle). Our analyses indicate that PldA of Pseudomonas aeruginosa, a eukaryotic-like phospholipase D (PLD), is a member of the Tle superfamily and the founding substrate of the haemolysin co-regulated protein secretion island II T6SS (H2-T6SS). While prior 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 inter-species bacterial interactions. Furthermore we find that this effector achieves its antibacterial activity by degrading phosphatidylethanolamine (PE), 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 ongoing evolution of pathogenesis.
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