Chelation of membrane-bound cations by extracellular DNA activates the type VI secretion system in pseudomonas aeruginosa

Pseudomonas aeruginosa employs its type VI secretion system (T6SS) as a highly effective and tightly regulated weapon to delivertoxic molecules to target cells. T6SS-secreted proteins of P. aeruginosa can be detected in the sputum of cystic fibrosis (CF)patients, who typically present a chronic and polymicrobial lung infection. However, the mechanism of T6SS activation in theCF lung is not fully understood. Here we demonstrate that extracellular DNA (eDNA), abundant within the CF airways, stimulatesthe dynamics of the H1-T6SS cluster apparatus in Pseudomonas aeruginosa PAO1. Addition of ^Mg2+ or DNase with eDNAabolished such activation, while treatment with EDTA mimicked the eDNA effect, suggesting that the eDNA-mediated effect isdue to chelation of outer membrane-bound cations. DNA-activated H1-T6SS enables P. aeruginosa to nonselectively attackneighboring species regardless of whether or not it was provoked. Because of the importance of the T6SS in interspecies interactionsand the prevalence of eDNA in the environments that P. aeruginosa inhabits, our report reveals an important adaptationstrategy that likely contributes to the competitive fitness of P. aeruginosa in polymicrobial communities.