Significance Specific bacterial communities colonize epithelial surfaces of most animals. In the last years many host mechanisms that control bacterial community composition have been identified. In contrast, only a few mechanisms are known that allow the host to target the behavior of its bacterial colonizers. We identified a eukaryotic mechanism based on an oxidoreductase activity, which enables the cnidarian Hydra to modify bacterial quorum-sensing (QS) molecules. The modification of QS signals leads to a phenotypic switch in the bacterial symbionts and promotes colonization of host tissue.