A Type VI Secretion System Trans-Kingdom Effector Is Required for the Delivery of a Novel Antibacterial Toxin in Pseudomonas aeruginosa
A Type VI Secretion System Trans-Kingdom Effector Is Required for the Delivery of a Novel Antibacterial Toxin in Pseudomonas aeruginosa
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DOI：
10.3389/fmicb.2019.01218
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发表时间：
2019-06-05
影响因子：
5.2
通讯作者：
Bleves, Sophie
中科院分区：
文献类型：
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作者：
Berni, Benjamin;Soscia, Chantal;Bleves, Sophie
铜绿假单胞菌已经进化出多种策略来解除和利用其宿主。为此目的，这种机会主义病原体特别发展了在周围介质中的蛋白质分泌或注射到宿主细胞中。其中，VI型分泌系统（T6 SS）用于将效应物递送到真核宿主以及靶细菌中。它组装成一个可收缩的噬菌体尾巴样结构，功能就像一个箭头，将一个装有效应器的箭头注入靶细胞。铜绿假单胞菌的T6 SS抗菌效应子的库非常广泛，以促进各种细菌群落中的环境适应和存活，并且可能也在真核宿主中。本文报道了铜绿假单胞菌Tle 3和Tli 3的一对新的抗菌效应子和免疫原的发现。Tli 3中和Tle 3在周质中的毒性以保护免于自相残杀中毒。Tle 3的分泌机制的表征表明，它需要细胞质衔接子Tla 3被靶向并加载到VgrG 2b刺突上，从而通过H2-T6 SS机制递送。Tla 3与迄今为止发现的其他衔接子不同，并在具有DUF 2875的T6 SS中定义了一个新的家族。有趣的是，这使我们发现，我们先前表征为抗真核效应子的VgrG 2b也具有抗菌活性，因为它对大肠杆菌有毒。令人兴奋的是，Tli 3可以抵消VgrG 2b毒性。因此，VgrG 2b是一种新的跨界效应子，靶向细菌和真核生物。VgrG 2b代表了在环境中和宿主感染的背景下对抗铜绿假单胞菌的一个有趣的靶标。
Pseudomonas aeruginosa has evolved multiple strategies to disarm and take advantage of its host. For this purpose, this opportunist pathogen has particularly developed protein secretion in the surrounding medium or injection into host cells. Among this, the type VI secretion system (T6SS) is utilized to deliver effectors into eukaryotic host as well as target bacteria. It assembles into a contractile bacteriophage tail-like structure that functions like a crossbow, injecting an arrow loaded with effectors into the target cell. The repertoire of T6SS antibacterial effectors of P. aeruginosa is remarkably broad to promote environmental adaptation and survival in various bacterial communities, and presumably in the eukaryotic host too. Here, we report the discovery of a novel pair of antibacterial effector and immunity of P. aeruginosa, Tle3 and Tli3. Tli3 neutralizes the toxicity of Tle3 in the periplasm to protect from fratricide intoxication. The characterization of the secretion mechanism of Tle3 indicates that it requires a cytoplasmic adaptor, Tla3, to be targeted and loaded onto the VgrG2b spike and thus delivered by the H2-T6SS machinery. Tla3 is different from the other adaptors discovered so far and defines a novel family among T6SS with a DUF2875. Interestingly, this led us to discover that VgrG2b that we previously characterized as an anti-eukaryotic effector possesses an antibacterial activity as well, as it is toxic towards Escherichia coli. Excitingly Tli3 can counteract VgrG2b toxicity. VgrG2b is thus a novel trans-kingdom effector targeting both bacteria and eukaryotes. VgrG2b represents an interesting target for fighting against P. aeruginosa in the environment and in the context of host infection.