The evolution of the type VI secretion system as a disintegration weapon
The evolution of the type VI secretion system as a disintegration weapon
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DOI：
10.1371/journal.pbio.3000720
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发表时间：
2020-05-01
期刊：
影响因子：
9.8
通讯作者：
Foster, Kevin R.
中科院分区：
文献类型：
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作者：
Smith, William P. J.;Vettiger, Andrea;Foster, Kevin R.
VI型分泌系统(T6SS)是许多细菌用来将携带毒素的针头插入其他细菌细胞的纳米机器。虽然影响细菌竞争的潜在因素是显而易见的，但使用T6SS对健康的影响还不是很清楚。在这里，我们提出了一个新的基于代理的模型，该模型能够详细研究T6SS武器在与其他细菌竞争时的进化成本和收益。我们的模型确定了T6SS的一个关键问题。由于其短距离，T6SS的活动变得自我限制，因为死亡细胞在其路径上积累，形成阻止进一步攻击的“僵尸屏障”。然而，对该模型的进一步探索为这个问题提供了解决方案：如果注射的毒素除了杀死靶细胞外，还能迅速溶解靶细胞，T6SS就会成为一种更有效的武器。我们用单细胞分析对携带T6SS的贝利不动杆菌和对T6SS敏感的大肠杆菌之间的战斗进行了验证。正如所预测的那样，裂解毒素的输送是非常有效的，而非裂解毒素会让大片的大肠杆菌存活下来。然后，我们使用已公布的基因组数据分析了数百种细菌，这些数据表明，绝大多数使用T6SS的细菌确实使用裂解毒素，这表明了武器进化的一般原理。我们的工作表明，在T6SS中，细菌已经进化出一种分解武器，其有效性往往取决于分解竞争对手的能力。了解细菌武器的进化功能有助于设计既能建立良好的问题物种又能消除问题物种的益生菌。
The type VI secretion system (T6SS) is a nanomachine used by many bacteria to drive a toxin-laden needle into other bacterial cells. Although the potential to influence bacterial competition is clear, the fitness impacts of wielding a T6SS are not well understood. Here we present a new agent-based model that enables detailed study of the evolutionary costs and benefits of T6SS weaponry during competition with other bacteria. Our model identifies a key problem with the T6SS. Because of its short range, T6SS activity becomes self-limiting, as dead cells accumulate in its way, forming "corpse barriers" that block further attacks. However, further exploration with the model presented a solution to this problem: if injected toxins can quickly lyse target cells in addition to killing them, the T6SS becomes a more effective weapon. We tested this prediction with single-cell analysis of combat between T6SS-wielding Acinetobacter baylyi and T6SS-sensitive Escherichia coli. As predicted, delivery of lytic toxins is highly effective, whereas nonlytic toxins leave large patches of E. coli alive. We then analyzed hundreds of bacterial species using published genomic data, which suggest that the great majority of T6SS-wielding species do indeed use lytic toxins, indicative of a general principle underlying weapon evolution. Our work suggests that, in the T6SS, bacteria have evolved a disintegration weapon whose effectiveness often rests upon the ability to break up competitors. Understanding the evolutionary function of bacterial weapons can help in the design of probiotics that can both establish well and eliminate problem species.