Zwittermicin A (ZwA), a hybrid polyketide-peptide antibiotic, and N-acyl -homoserine-lactonase (AHL-lactonase), a kind of quorum-quenching enzyme, have the potential to prevent the virulence of Erwinia carotovora, which is a major pathogen of soft rot. The purpose of this study was to combine the two agents in one host to improve their prevention efficacy. AHL-lactonase was over-expressed in the ZwA-producing strain Bacillus cereus and derivates were identified to create genetically modified (GM) strains. The comparative results showed that neither ZwA nor AHL-lactonase impacted the yield of the other; the increased yield of ZwA could promote the prevention efficacy of GM strains; Coexistence of ZwA and AHL-lactonase in the GM strains had better prevention efficacy than either has separately. It is a potential therapy to provide more effective prevention and withstand gradually increasing pesticide-resistance by combining the two antibacterial agents.