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RovC - a novel type of hexameric transcriptional activator promoting type VI secretion gene expression.Knittel, Vanessa; Sadana, Pooja; Seekircher, Stephanie; Stolle, Anne-Sophie; Körner, Britta; Volk, Marcel; Jeffries, Cy M; Svergun, Dmitri I; Heroven, Ann Kathrin; Scrima, Andrea; et al. (PLOS, 2020-09-23)Type VI secretion systems (T6SSs) are complex macromolecular injection machines which are widespread in Gram-negative bacteria. They are involved in host-cell interactions and pathogenesis, required to eliminate competing bacteria, or are important for the adaptation to environmental stress conditions. Here we identified regulatory elements controlling the T6SS4 of Yersinia pseudotuberculosis and found a novel type of hexameric transcription factor, RovC. RovC directly interacts with the T6SS4 promoter region and activates T6SS4 transcription alone or in cooperation with the LysR-type regulator RovM. A higher complexity of regulation was achieved by the nutrient-responsive global regulator CsrA, which controls rovC expression on the transcriptional and post-transcriptional level. In summary, our work unveils a central mechanism in which RovC, a novel key activator, orchestrates the expression of the T6SS weapons together with a global regulator to deploy the system in response to the availability of nutrients in the species' native environment.