关键词: 枯草芽孢杆菌素, 金黄色葡萄球菌 , 抑菌活性, 绝对致死剂量

Abstract: 【Objective】 In order to provide the theoretical basis for clinical application of the bacteriocin Subticin112 secreted by Bacillus subtilis, a research was conducted on bacteriostatic activity of bacteriocin Subticin112 against Staphylococcus aureus CVCC 1885 in vitro and in vivo. 【Method】 Bacteriostasis in vitro: Subticin112, oxytetracycline, penicillin, vancomycin, neomycin, strepomycin and gentamicin in the same effective weight were dissolved into equal volume of sterile saline, respectively. Then the agar diffusion method was used to compare the bacteriostatic activity of the medicines against S. aureus. Bacteriostasis in vivo: 120 SPF-class KM male mice (weighted from 18 g to 22 g) were divided into six groups, they were blank control group, negative control group, oxytetracycline treating group and three Subticin112 treating groups. After the beginning of the experiment, every mouse in each group was orallly administrated 0.4 mL different concentrations of medicine or sterile saline every other 8 hours, after 3 times of oral administration, the mice in each group were intraperitoneal injected at the absolute lethal dose of S. aureus or sterile saline. At the end of the experiment, the mortality was calculated, the proinflammatory cytokines and the cfu values of S. aureus in the peritoneum of the mice were determined, and then the histopathological changes of the tissues were observed. 【Result】Bacteriostasis in vitro: Subticin112 expressed a fine bacteriostatic activity compared to the same concentration of other medicines. The bacteriostatic activity of Subticin112 was highly significantly better than that of vancomycin and neomycin (P＜0.01), but differed insignificantly from other antibiotics (P＞0.05). Bacteriostasis in vivo: after the experiment, the mortality in negative control group was 100%, while which was 30% in low-dose Subticin112 treating group, and other groups did not have dead mice. The medicine treating groups showed a low concentration of the proinflammatory cytokines (P＜0.05), also had a low cfu values compared to the negative control group (P＜0.01) and the dose-respones relationship was clear. The histopathological observations showed that the liver and spleen of the mice in the negative control group had obvious pathological lesions, whereas the pathological changes in the medicine treating groups was slight or not distinct. 【Conclusion】These studies provided evidences that Subticin112 have a fine bacteriostatic activity against S. aureus CVCC 1885 in vitro and vivo, and can be developed as a new type of antibacterial agent.

Key words: Bacillus subtilis bacteriocin, Staphylococcus aureus, bacteriostatic activity, absolute lethal dose