Specialized killing across the domains of life by the type VI secretion systems of Pseudomonas aeruginosa

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.