Abstract:[Background] Staphylococcus aureus is a key reason for the increase in the global drug resistance burden. Bacteriocins produced by lactic acid bacteria are a new method to treat pathogenic bacterial infections and has broad application prospects. [Objective] To screen the bacteriocins of lactic acid bacteria that inhibit S. aureus. [Methods] The agar diffusion method was used to screen the bacteriocin-producing lactic acid bacteria. Strains were identified by 16S rRNA gene sequencing and a phylogenetic tree was constructed using MEGA 11. After the effects of acids and hydrogen peroxide were excluded, the anti-enzymolysis property, pH stability, and thermostability of the bacteriocin produced by this strain were characterized. The growth curve, acid production capacity, and tolerance to simulated gastric fluid of the strain were studied. [Results] A strain named Leuconostoc mesenteroides WJY-6 was isolated from pumpkin in Yanji. It secreted a bacteriocin showing inhibitory effects on S. aureus from different sources. The bacteriocin exhibited a good anti-enzymolysis property and maintained over 35% of the inhibitory effect after being treated at 100 ℃ and 121 ℃. The bacteriocin showcased the strongest inhibitory activity at pH 3.0-5.0. The strain entered a stable growth phase after 18 h, with the pH dropping below 5.0 after 8 h, which steadily improved the inhibitory effect. The strain showed strong survival ability and proliferated actively in the simulated gastric fluid. [Conclusion] L. mesenteroides WJY-6 has a strong acid production ability and good tolerance to simulated gastric fluid. Moreover, it secretes a bacteriocin with excellent physical and chemical properties and inhibitory effect on S. aureus. The bacteriocin is expected to become a new alternative of antibiotics for the prevention and treatment of S. aureus.