Tomato-derived melatonin targets the CpxA CpxR two-component system to inhibit virulence of pathogenic bacteria

Plants deploy a variety of secondary metabolites and signaling molecules to fend off pathogen attack. As a inter-kingdom signaling molecule throughout organisms, the exact mechanisms of melatonin in plant-pathogen interaction are often unknown. Using tomato (Solanum lycopersicum) and Pseudomonas syringae pv. tomato DC3000 (Pst DC3000) as plant-pathogen interaction models, this study shows that the plant-derived melatonin functions primarily by inhibiting bacterial type III secretion system (T3SS) genes expression to reduce bacterial virulence and pathogenicity. In detail, bacterial CpxA interacts with melatonin through G48 and T51 residues located in the periplasmic sensor domain. This interaction inhibits autophosphorylation of CpxA and transphosphorylation of CpxR, blocking the cascade phosphorylation of the CpxA/CpxR two-component system. The DNA-binding capacity of CpxR to promoters of T3SS genes is weakened by reduced cascade phosphorylation of CpxA/CpxR, inhibiting bacterial T3SS genes expression, virulence and pathogenicity. Therefore, CpxA can be defined as a sensor that senses plant-derived melatonin in plant-pathogen interaction. Genetic engineering of phytomelatonin synthesis can obtain persistent resistance and crop productivity. Collectively, these results illustrate a previously unknown mechanism by which plants disarm a pathogenic bacteria, as well as provide effective molecular targets for crop genetic improvement and biopesticides development.