Effectiveness of Pseudomonas aeruginosa type VI secretion system relies on toxin potency and type IV pili-dependent interaction

Abstract

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.

Type 1 fimbriae-mediated collective protection against type 6 secretion system attacks

“…The product of these genes would thus impact how attacker and target cells interact together. This suggests that the modulation of the interaction dynamics between attacker and target cells could be a main strategy by which target cells can evade T6SS attacks ( 28 , 29 , 59 , 60 ). Another hit that exhibited resistance to T6SS activity is the ldtB mutant.…”

Interactions between pili affect the outcome of bacterial competition driven by the type VI secretion system

“…It is estimated to be found in more than 25% of gram-negative bacteria, encompassing both environmental and pathogenic species [12]. The delivery of T6SS toxins has been shown to influence microbial population compositions [13][14][15]. Importantly, the spatial arrangement of competing cells also impacts the effectiveness of the T6SS [13,16].…”