A sub-MIC 200 U/ml concentration of nisin was used to clarify the antibacterial role of nisin in drug combinations. This concentration was significantly less than the MIC of nisin against the three E. faecalis strains and alone could not inhibit the bacterial growth, as the MICs of ATCC 29212, OG1RF, and strain E were found to be 1,000 U/ ml. In the evaluation of bacterial survival rates, penicillin, chloramphenicol, and linezolid in combination with nisin could completely kill E. faecalis. This bactericidal effect was not due to the action of 200 U/ml nisin alone, but evidently nisin improves the bactericidal activities of these antibiotics. Especially with the addition of nisin, the low concentration of 16 mg/L penicillin resulted in complete bactericidal activity. Many studies have indicated that nisin exerts its bactericidal activity by forming pores and inhibiting cell wall synthesis with a specific molecule, Lipid II, a principal component of the membranes of gram-positive bacteria. Nisin uses Lipid II as a “docking molecule” to form pores on the cell membrane surface in a targeted manner; at a nanomolar level, then, nisin is able to effectively kill bacteria. Therefore, 200 U/ml nisin is sufficient to form pores on the surface of bacteria and to facilitate the penetration of other antibiotic molecules into the microorganisms. In this way, antibiotics will better capture the antibacterial effects when their antibacterial action is occurring intracellularly. For example, macrolide antibiotics binds irreversibly to a site on the 50S subunit of the bacterial ribosome and inhibits the translocation steps of protein synthesis. Quinolone prevents bacterial DNA from unwinding and duplicating. Aminoglycoside antibiotics work by binding to the bacterial 30S R428 supply ribosomal subunit and inhibiting protein synthesis, and thereby compromise the structure of the bacterial cell wall, etc. The antibacterial activities of these antibiotics were obviously improved in the presence of a low concentration of nisin, 200 U/ml. This synergetic antibacterial mechanism involving the intracellular and cell membranes has been demonstrated in previous studies. The pores made by nisin allow more fluoride ions to enter Streptococcus mutans and for more doxycycline molecules to penetrate into E. faecalis; these actions result in the synergetic antibacterial activities of nisin and sodium fluoride, as well as of nisin and doxycycline. Furthermore, the study by Cottagnoud et al. showed that the cell wall disruption induced by vancomycin acts synergistically with gentamicin against penicillin-resistant pneumococci by increasing the intracellular penetration of gentamicin. Nevertheless, 200 U/ml nisin was not sufficient to facilitate E. faecalis inhibition by sulfapyridine, metronidazol, or polymyxin. This may be due to the intrinsic resistance of E. faecalis to the three antibiotics.