Mutant Selection Windows of Azalomycin F 5a in Combination with Vitamin K 3 against Methicillin-Resistant Staphylococcus aureus
Mutant Selection Windows of Azalomycin F 5a in Combination with Vitamin K 3 against Methicillin-Resistant Staphylococcus aureus
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DOI：
10.4236/jbm.2016.412020
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发表时间：
2016-12
期刊：
影响因子：
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通讯作者：
Xuejie Xu;Xuejiao Wu;Ganjun Yuan;Li Xu;Yimin Wang
中科院分区：
文献类型：
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作者：
Xuejie Xu;Xuejiao Wu;Ganjun Yuan;Li Xu;Yimin Wang
阿扎霉素F5 a是一种从多种链球菌中分离得到的36元大环内酯，具有显著的抗耐甲氧西林金黄色葡萄球菌（MRSA）活性。为了提高其抗MRSA的潜力并在开发前评估MRSA对其耐药的可能性，首先使用棋盘测定法评估阿扎霉素F5 a与维生素K3组合的抗MRSA活性。然后使用具有线性抗菌剂浓度降低的琼脂平板测定阿扎霉素F5 a单独和与维生素K3组合对MRSA的99%抑制菌落形成的最小浓度（MIC 99）和突变预防浓度（MPC）。分数抑制浓度指数（FICI）为0.25 - 0.50，显示阿扎霉素F5 a与维生素K3组合的协同活性。阿扎霉素F5 a单药对MRSA的突变体选择窗口（MSWs，MIC 99-MPC）为2.07 ~ 6.40 μg/mL，阿扎霉素F5 a与维生素K3联用对MRSA的MPCs为1.60 ~ 3.20 μg/mL。这些表明阿扎霉素F5 a组合的MPC可下降至低于其单独的MIC 99。根据MSW假说，阿扎霉素F5 a单独使用的MSW较窄，甚至与维生素K3组合的MSW接近，以及它们的协同抗MRSA活性，表明阿扎霉素F5 a具有良好的开发潜力作为一种新的抗菌剂。
Azalomycin F5a, a 36-membered macrocyclic lactone isolated from several streptomyces strains, presented remarkable anti-methicillin-resistant Staphylococcus aureus (MRSA) activities. To improve its anti-MRSA potential and to evaluate the probability of MRSA resistant to it before development, the anti-MRSA activities of azalomycin F5a in combination with vitamin K3 were first evaluated using checkerboard assay. Then the minimal concentration inhibiting colony formation by 99% (MIC99) and mutant prevention concentration (MPC) of azalomycin F5a alone and in combination with vitamin K3 against MRSA were determined using agar plates with linear antimicrobial concentration decrease. The fractional inhibitory concentration indexes (FICIs) of 0.25 - 0.50 showed the synergistic activity of azalomycin F5a in combination with vitamin K3. The mutant selection windows (MSWs, MIC99-MPC) of azalomycin F5a alone against MRSA tested were 2.07 - 6.40 μg/mL, and the MPCs of azalomycin F5a in combination with vitamin K3 against MRSA tested were 1.60 - 3.20 μg/mL. These indicated that the MPCs of azalomycin F5a in combination could drop down to below its MIC99 alone. According to the hypothesis of MSW, the narrower MSWs of azalomycin F5a alone, even closed MSWs in combination with vitamin K3, together with their synergistic anti-MRSA activities, indicated that azalomycin F5a had a good potential to develop as a new antimicrobial agent.