[Erh-Min Lai] TagF-mediated T6SS repression in two distinct bacterial pathogens
The type VI secretion system (T6SS) mainly delivers effectors into eukaryotic host cells or toxins into competitor bacterial cells for survival. T6SS is positively regulated by the threonine phosphorylation pathway (TPP) and negatively by the T6SS-accessory protein TagF. In this study, Erh-Min Lai’s laboratory studied the mechanisms underlying TagF-mediated T6SS repression in two distinct bacterial pathogens, Agrobacterium tumefaciens and Pseudomonas aeruginosa (Lin et al., Journal of Biological Chemistry, 2018). They found that in A. tumefaciens, T6SS activity is suppressed by a chimeric protein consisting of TagF and the PppA phosphatase. Remarkably, this TagF domain is sufficient to post-translationally repress the T6SS, and this inhibition is independent of TPP but requires interaction with a cytoplasmic protein, Fha, critical for activating T6SS assembly. In addition, P. aeruginosa TagF also interacted with Fha1, suggesting that this interaction represents a conserved TagF-mediated regulatory mechanism. Using TagF variants with substitutions of conserved amino acid residues at predicted protein–protein interaction interfaces, they uncovered evidence that the TagF–Fha interaction is critical for TagF-mediated T6SS repression in both bacteria. TagF inhibited T6SS without affecting T6SS protein abundance in A. tumefaciens, but TagF overexpression reduced the protein levels of all analyzed T6SS components in P. aeruginosa. Our results indicate that TagF interacts with Fha, but this in turn seems to impact different stages of T6SS assembly in different bacteria, possibly reflecting evolutionary divergence in T6SS control.