Abstract:The mechanism of metal antimicrobial peptide SIF4 against cell permeability of Staphylococcus aureus (S.aureus) was explored based on extracellular alkaline phosphatase activity (AKP), cell surface potential (CSP), cell surface hydrophobicity (CSH), cell inner membrane permeability (CIMP) and intracellular macromolecular leakage (IML). The results showed that SIF4 could destroy cell wall structural integrity. With the increasing of antibacterial peptide concentration and incubation time, the activity of extracellular AKP also increased simultaneously, and there was insignificant difference between 2MIC group and TritonX-100 group (P>0.05). The SIF4 concentration had a negative correlation with CSP, and a good dose-effect positive correlation with CSH. Moreover, CIMP and IML had a positive correlation with the antibacterial peptide concentration and incubation time. There was a significant difference in IML (P<0.05) after incubation for 1 h, while there was insignificant difference between the 2MIC and TritonX-100 groups(P>0.05) after 3 h incubation. The findings suggested that SIF4 could enhance cell permea- bility, cause IML leakage, enhance CSH and reduce CSP, inducing cell aggregation and apoptosis.