奥扎尼莫德抑制金黄色葡萄球菌生长和生物被膜形成的研究

The inhibitory effect of ozanimod on the growth and biofilm formation of Staphylococcus aureus

目的拟筛选可抑制金黄色葡萄球菌(以下简称“金葡菌”)生长和生物被膜形成的新型化合物。方法通过96孔板法从美国FDA已经批准上市药物化合物库中筛选可抑制金葡菌生长的化合物。通过酶标仪测定600 nm波长吸光度值(OD600)以检测培养上清液中浮游菌含量。通过微量肉汤稀释法检测奥扎尼莫德对临床分离金葡菌株的最低抑菌浓度(minimum inhibitory concentration,MIC)。通过结晶紫染色法检测亚抑菌浓度奥扎尼莫德对金葡菌生物被膜形成的抑制作用。结果本研究筛选发现奥扎尼莫德可显著抑制金葡菌SA113株(筛选参考菌株)的生长,MIC为25.00μmol/L。奥扎尼莫德对119株金葡菌临床株[甲氧西林敏感株(MSSA)为65株,耐甲氧西林株(MRSA)为54株]的MIC为12.50或25.00μmol/L,MIC_(50)和MIC_(90)均为25.00μmol/L。本研究发现6.25μmol/L、12.50μmol/L、25.00μmol/L的奥扎尼莫德显著抑制了2株MSSA和2株MRSA生物被膜形成。亚抑菌浓度奥扎尼莫德(12.50μmol/L)显著抑制了14株MSSA和11株MRSA生物被膜形成,但对这些菌株的浮游菌生长无抑制作用。结论奥扎尼莫德可抑制金葡菌包括MRSA的生长,具有良好的抑菌活性。亚抑菌浓度的奥扎尼莫德可显著抑制金葡菌的生物被膜形成。

Objective To screening new compounds that can inhibit the growth and biofilm formation of Staphylococcus aureus.Methods Compounds that can inhibit the growth of Staphylococcus aureus were screened from the FDA approved drug library by 96 well plates.The absorbance value of 600 nm wavelength(OD_(600))was measured by Microplate Reader to detect the growth of Staphylococcus aureus planktonic cells in the culture supernatant.The minimum inhibitory concentration(MIC)of ozanimod against Staphylococcus aureus clinical isolates were detected by micro broth dilution method.The inhibitory effect of sub-inhibitory concentrations of ozanimod on the biofilm formation of Staphylococcus aureus was detected by crystal violet staining.Results This study found that ozanimod could significantly inhibit the growth of Staphylococcus aureus SA113(screening reference strain),and the MIC_(50) was 25.00μmol/L.The MIC_(50) of ozanimod against 119 clinical isolates of Staphylococcus aureus[65 isolates of methicillin sensitive(MSSA)and 54 isolates of methicillin resistant(MRSA)]was 12.50 or 25.00μmol/L.The MICand MICof ozanimod against the 119 Staphylococcus aureus isolates all were 25.00μmol/L.Thisstudy found that 6.25,12.50,25.00μmol/L of ozanimod could significantly inhibit the biofilm formation of 2 MSSA and 2 MRSA.The sub-MIC concentration of ozanimod(12.50μmol/L)could significantly inhibit the biofilm formation of 14 MSSA and 11 MRSA,but had no inhibitory effect on the growth of planktonic cells of these Staphylococcus aureus isolates.Conclusion Ozanimod can inhibit the growth of Staphylococcus aureus,including MRSA,and has good antibacterial activity.The sub-MIC concentration of ozanimod could significantly inhibit the biofilm formation of Staphylococcus aureus.