Abstract：
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.
摘要：
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,尚未报道在竞争细菌中注射的细菌效应子破坏超过单个靶标的情况。这里,我们证明了效应蛋白，Ltae,通过IV型分泌系统（T4SS）从土壤细菌溶菌酶基因转移到竞争细菌中，假单胞菌蛋白原,影响几个目标，从而使竞争对手的抗菌防御系统失效。一个LtaE靶标是转录因子，LuxR1，调节抗菌化合物的生物合成，另一个目标是sigma因子，PvdS,生物合成另一种抗菌化合物所需的，pyoverdine.参与orfamideA和pyoverdine生物合成的基因的缺失使P.蛋白原的抗菌活性失效，而LtaE在P.蛋白原中的表达导致对L.酶基因的抗菌活性几乎完全丧失。机械上,LtaE抑制RNA聚合酶复合物与这些蛋白质中的每一种的组装。LtaE与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中存在的各种竞争者的防御。因此，我们的研究表明，多靶标效应子不仅在真核宿主中而且在细菌竞争者中都已进化为抑制细胞防御。
