Effector proteins secreted by bacteria that infect mammalian and plant cells often subdue eukaryotic host cell defenses by simultaneously affecting multiple targets. However, instances when a bacterial effector injected in the competing bacteria sabotage more than a single target have not been reported. Here, we demonstrate that the effector protein, LtaE, translocated by the type IV secretion system (T4SS) from the soil bacterium Lysobacter enzymogenes into the competing bacterium, Pseudomonas protegens, affects several targets, thus disabling the antibacterial defenses of the competitor. One LtaE target is the transcription factor, LuxR1, that regulates biosynthesis of the antimicrobial compound, orfamide A. Another target is the sigma factor, PvdS, required for biosynthesis of another antimicrobial compound, pyoverdine. Deletion of the genes involved in orfamide A and pyoverdine biosynthesis disabled the antibacterial activity of P. protegens, whereas expression of LtaE in P. protegens resulted in the near-complete loss of the antibacterial activity against L. enzymogenes. Mechanistically, LtaE inhibits the assembly of the RNA polymerase complexes with each of these proteins. The ability of LtaE to bind to LuxR1 and PvdS homologs from several Pseudomonas species suggests that it can sabotage defenses of various competitors present in the soil or on plant matter. Our study thus reveals that the multi-target effectors have evolved to subdue cell defenses not only in eukaryotic hosts but also in bacterial competitors.

中文翻译：

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IV型分泌系统效应器破坏竞争细菌中的多个防御系统


感染哺乳动物和植物细胞的细菌分泌的效应蛋白通常通过同时影响多个靶标来抑制真核宿主细胞的防御。然而，尚未报道将细菌效应子注射到竞争细菌中破坏多个目标的情况。在这里，我们证明效应蛋白 LtaE 通过 IV 型分泌系统 (T4SS) 从土壤细菌溶酶杆菌转位到竞争细菌保护假单胞菌中，影响多个靶标，从而禁用竞争对手的抗菌防御。 LtaE 的一个靶标是转录因子 LuxR1，它调节抗菌化合物 Orfamide A 的生物合成。另一个靶标是 Sigma 因子 PvdS，它是另一种抗菌化合物 Pyoverdine 生物合成所需的。删除与orfamide A和pyoverdine生物合成有关的基因使P. protegens的抗菌活性失效，而P. protegens中LtaE的表达导致对L. enzymogenes的抗菌活性几乎完全丧失。从机制上讲，LtaE 抑制 RNA 聚合酶复合物与这些蛋白质的组装。 LtaE 与来自几种假单胞菌属物种的 LuxR1 和 PvdS 同源物结合的能力表明，它可以破坏土壤或植物上存在的各种竞争者的防御。因此，我们的研究表明，多靶点效应器已经进化到不仅可以抑制真核宿主的细胞防御，还可以抑制细菌竞争者的细胞防御。