Effectiveness of Pseudomonas aeruginosa type VI secretion system relies on toxin potency and type IV pili-dependent interaction.
Effectiveness of Pseudomonas aeruginosa type VI secretion system relies on toxin potency and type IV pili-dependent interaction.
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DOI：
10.1371/journal.ppat.1011428
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发表时间：
2023-05
期刊：
影响因子：
6.7
通讯作者：
中科院分区：
文献类型：
--
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VI型分泌系统（T6 SS）是一种抗菌武器，被许多革兰氏阴性细菌使用，通过将毒素注入相邻的猎物细胞来获得竞争优势。预测依赖T6 SS的竞争的结果不仅依赖于系统的存在-不存在，而是涉及多种因素。铜绿假单胞菌具有3种不同的T6 SS和一组20多种具有不同功能的毒性效应物，包括破坏细胞壁完整性、降解核酸或代谢损伤。我们产生了具有不同程度的T6 SS活性和/或对每个单独的T6 SS毒素的敏感性的突变体的综合集合。通过对整个混合细菌大菌落进行成像，我们研究了这些铜绿假单胞菌菌株如何在多个攻击者/猎物组合中获得竞争优势。我们观察到单个T6 SS毒素的效力彼此显著不同，如通过监测群落结构所测量的，其中一些毒素在协同作用中起更好的作用或需要更高的有效载荷。值得注意的是，猎物和攻击者之间的混合程度也是竞争结果的关键，并且由接触的频率以及猎物使用IV型纤毛依赖性抽搐运动远离攻击者的能力所驱动。最后，我们实现了一个计算模型，以更好地理解T6 SS放电行为或细胞-细胞接触的变化如何导致群体水平的竞争优势，从而提供适用于所有类型的基于接触的竞争的概念性见解。VI型分泌系统（T6 SS）是在革兰氏阴性菌中发现的，是一种接触依赖性分子纳米机器，可将抗菌毒素注入竞争对手。T6 SS活性为生物体在给定的生态位中占优势提供了竞争优势。注射毒素的数量和生化活性可能因细菌种类而异。条件致病菌铜绿假单胞菌是相当多产的，具有超过20种特征性和不同的T6 SS毒素。在这里，我们通过实验解决了T6 SS活性程度的重要性，并证明了许多铜绿假单胞菌T6 SS毒素计数中的每一个。没有冗余，而是有时协同作用，这支持注射混合毒素而不是特定毒素的子集的有效性。由于接触是T6 SS传递的关键因素，我们进一步观察到，能够使用表面运动技能逃离细菌攻击者的猎物有更好的繁殖和生存机会。进一步的实验方法，我们使用计算建模将这些数据的背景下，混合铜绿假单胞菌种群。通过这种方式，我们有助于理解个体之间基于接触的高度局部相互作用如何塑造整个细菌群落的结构。
The type VI secretion system (T6SS) is an antibacterial weapon that is used by numerous Gram-negative bacteria to gain competitive advantage by injecting toxins into adjacent prey cells. Predicting the outcome of a T6SS-dependent competition is not only reliant on presence-absence of the system but instead involves a multiplicity of factors. Pseudomonas aeruginosa possesses 3 distinct T6SSs and a set of more than 20 toxic effectors with diverse functions including disruption of cell wall integrity, degradation of nucleic acids or metabolic impairment. We generated a comprehensive collection of mutants with various degrees of T6SS activity and/or sensitivity to each individual T6SS toxin. By imaging whole mixed bacterial macrocolonies, we then investigated how these P. aeruginosa strains gain a competitive edge in multiple attacker/prey combinations. We observed that the potency of single T6SS toxin varies significantly from one another as measured by monitoring the community structure, with some toxins acting better in synergy or requiring a higher payload. Remarkably the degree of intermixing between preys and attackers is also key to the competition outcome and is driven by the frequency of contact as well as the ability of the prey to move away from the attacker using type IV pili-dependent twitching motility. Finally, we implemented a computational model to better understand how changes in T6SS firing behaviours or cell-cell contacts lead to population level competitive advantages, thus providing conceptual insight applicable to all types of contact-based competition. The Type VI Secretion System (T6SS) was discovered in Gram-negative bacteria and is a contact-dependent molecular nanomachine which injects antimicrobial toxins into competitors. The T6SS activity provides a competitive edge for an organism to prevail in a given niche. The number and biochemical activity of toxins injected could vary from one bacterial species to the other. The opportunistic pathogen Pseudomonas aeruginosa is quite prolific with more than 20 characterized and distinct T6SS toxins. Here we experimentally addressed the importance in the degree of T6SS activity and made the demonstration that every single of the many P. aeruginosa T6SS toxin counts. There are no redundancies and instead on occasion synergies, which support the effectiveness of injecting a cocktail of toxins rather than a subset of specific ones. Since contact is a key factor for T6SS delivery, we further observed that preys able to use surface motility skills to run away from bacterial attackers have better chances to multiply and survive. Furthering experimental approaches, we used computational modelling to place these data in the context of a mixed P. aeruginosa population. This way we contribute understanding to how highly local contact-based interactions between individuals shape the structure of whole bacterial communities.
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