重组溶葡球菌酶的体外抗菌活性研究

Evaluation of recombinant lysostaphin activities in vitro against Staphylococci

目的:评价重组溶葡球菌酶对545株临床分离葡萄球菌的体外抗茵活性。方法:采用平皿二倍稀释法,测定重组溶葡球菌酶对545株葡萄球菌的最低抑菌浓度(MIC);采用试管二倍稀释法和平皿计数法测定此酶对45株葡萄球菌的最低杀菌浓度(MBC);采用不同浓度重组溶葡球菌酶不同时间的杀菌结果绘制杀菌曲线,检测其对4株受试葡萄球菌的动态杀菌趋势;此外,测定不同培养条件对MIC的影响。结果:此酶对257株金葡球菌具有较强的体外抗菌活性,对288株凝固酶阴性葡萄球菌的抗菌活性相对较弱;结合MBC和杀菌曲线结果,可以判断此酶对敏感菌为快速杀菌作用,并呈浓度依赖性;pH,细菌接种量及高浓度血清蛋白对MIC有一定影响,受试浓度的二价金属离子对MIC影响不明显。结论:重组溶葡球菌酶主要对金葡菌体现强大的抗菌活性,对耐甲氧西林金葡菌(MRSA)和甲氧西林敏感金葡菌(MSSA)的抗菌作用没有明显差别,有进一步研究的价值。

Objective：To determine the in vitro activity of recombinant lysostaphin against 545 strains of Staphylococci clinically isolated. Methods： An agar dilution method was used for determination of the MICs of recombinant lysostaphin and other antimicrobial agents against all isolates. A broth dilution method was used for determination of MBCs of recombinant lysostaphin against 45 isolates of Staphylococci. The eradication curve to bacteria was plotted by concentration variables of recombinant lysostaphin versus dynamic eradication of four isolates of Staphylococci at certain timepoints. The impacts of culture environments on the MIC of recombinant lysostaphin were assessed. Results ： Compared to the control antimicrobials, the recombinant lysostaphin showed more potent activities in vitro against 257 isolates of S. aureus and non-significant potent values against 288 isolates of coagulase-negative Staphylococci. The MBC and eradication curve studies found that the lysostaphin featured a rapid sterilization against the isolates of S. aureus in a concentration-dependent manner. Other factors, such as pH, inoculation size and highly concentrated serum, moderately impacted the MIC levels, and three bivalent cations were inactive on the MICs of lysostaphin. Conclusion： The lysostaphin is active against S. aureus and had a low propensity for selection of MRSA and MSSA organisms.