Compared to the surrounding soil, the root microbiome is limited in diversity, dominated by plant-recruited microbes. In this study we report that the commensal soil bacterium Dyella japonica secretes a protease—immunosuppressive subtilase A (IssA)—to dampen plant defenses and establish itself as part of the root microbiome by converting the immunity-eliciting peptide flg22 from a receptor agonist to an antagonist. A screen of 165 root-associated bacteria demonstrated that 67 strongly suppress flg22-induced activation of plant immunity in bioassays. These results, combined with a clue from the literature, identified D. japonica IssA as potentially involved in this suppression. To test this prediction, IssA was produced recombinantly and purified. Purified IssA suppressed flg22 activation in bioassays and cleaved flg22 in vitro. IssA cleaved flg22 at specific peptide bonds to create derivative peptides that are known to bind flg22 receptors without activating an immune response. While this research was performed on a model system, discovering how plants interact with the microbiome promises to generate new solutions for reducing wheat and barley scab.