Colautti Jake, Kelly Steven D, Whitney John C
Michael DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, ON, L8S 4K1, Canada.
Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, L8S 4K1, Canada.
Biochem J. 2025 Jan 8;482(1):1-15. doi: 10.1042/BCJ20230240.
Type VI secretion systems (T6SSs) are widespread bacterial protein secretion machines that inject toxic effector proteins into nearby cells, thus facilitating both bacterial competition and virulence. Pseudomonas aeruginosa encodes three evolutionarily distinct T6SSs that each export a unique repertoire of effectors. Owing to its genetic tractability, P. aeruginosa has served as a model organism for molecular studies of the T6SS. However, P. aeruginosa is also an opportunistic pathogen and ubiquitous environmental organism that thrives in a wide range of habitats. Consequently, studies of its T6SSs have provided insight into the role these systems play in the diverse lifestyles of this species. In this review, we discuss recent advances in understanding the regulation and toxin repertoire of each of the three P. aeruginosa T6SSs. We argue that these T6SSs serve distinct physiological functions; whereas one system is a dedicated defensive weapon for interbacterial antagonism, the other two T6SSs appear to function primarily during infection. We find support for this model in examining the signalling pathways that control the expression of each T6SS and co-ordinate the activity of these systems with other P. aeruginosa behaviours. Furthermore, we discuss the effector repertoires of each T6SS and connect the mechanisms by which these effectors kill target cells to the ecological conditions under which their respective systems are activated. Understanding the T6SSs of P. aeruginosa in the context of this organism's diverse lifestyles will provide insight into the physiological roles these secretion systems play in this remarkably adaptable bacterium.
VI型分泌系统（T6SSs）是广泛存在的细菌蛋白分泌机器，可将毒性效应蛋白注入附近细胞，从而促进细菌竞争和毒力。铜绿假单胞菌编码三种进化上不同的T6SSs，每种都输出独特的效应蛋白库。由于其遗传易处理性，铜绿假单胞菌已成为T6SS分子研究的模式生物。然而，铜绿假单胞菌也是一种机会致病菌和普遍存在的环境生物，能在广泛的栖息地中茁壮成长。因此，对其T6SSs的研究有助于深入了解这些系统在该物种不同生活方式中所起的作用。在本综述中，我们讨论了在理解铜绿假单胞菌三种T6SSs各自的调控和毒素库方面的最新进展。我们认为这些T6SSs具有不同的生理功能；其中一个系统是用于细菌间拮抗作用的专用防御武器，而另外两个T6SSs似乎主要在感染过程中发挥作用。我们在研究控制每个T6SS表达并协调这些系统与铜绿假单胞菌其他行为的信号通路时，为该模型找到了支持。此外，我们讨论了每个T6SS的效应蛋白库，并将这些效应蛋白杀死靶细胞的机制与各自系统被激活的生态条件联系起来。在这种生物多样的生活方式背景下理解铜绿假单胞菌的T6SSs，将有助于深入了解这些分泌系统在这种适应性极强的细菌中所起的生理作用。
