新型氟喹诺酮衍生物对水产致病菌及其生物被膜的抑制作用研究

Novel fluoroquinolone derivatives inhibit growth and biofilm formation of pathogenic bacteria in aquatic animals

【目的】细菌的耐药性给动物抗感染和疾病治疗带来了极大的困难和挑战,生物被膜是导致细菌耐药性的主要原因之一,本研究检测分析了氯丙酰基克林沙星对7株菌株的抗菌活性及其生物被膜形成能力,以期发现氯丙酰基克林沙星是否具有抗菌活性。【方法】本研究通过打孔法和微量肉汤二倍稀释法进行常规药敏试验以测定最小抑菌浓度(minimum inhibitory concentration,MIC)和最小杀菌浓度(minimum bactericidal concentration,MBC),通过结晶紫染色法检测这7株受试菌在药物亚抑菌浓度下的生物被膜形成能力以及生长速率来测定氯丙酰基克林沙星的抑菌能力。【结果】实验结果显示,氟喹诺酮类衍生物氯丙酰基克林沙星药物对4株受试革兰氏阴性菌的MIC≤10 mg/L、MBC≤48 mg/L,对3株受试革兰氏阳性菌也呈现敏感状态(MIC≤10 mg/L,MBC≤10 mg/L)。结晶紫染色法检测发现,这7株受试菌在药物亚抑菌浓度下的生物被膜形成能力以及生长速率显著下降,说明氯丙酰基克林沙星在亚抑菌浓度即具有良好的抑菌活性。【结论】本研究证明氯丙酰基克林沙星可用作抗菌剂,并为新型生物被膜抗菌剂或细菌感染治疗药物的开发提供了新的依据。

[Objective]The antibiotic resistance poses great challenges to the prevention and treatment of bacterial infections in animals,and biofilm formation is one of the main factors inducing the resistance.We determined the effects of chloropropanoyl clinafloxacin on the growth and biofilm formation of seven strains of bacteria,with a view to finding out whether chloropropanoyl clinafloxacin has antibacterial activity.[Methods]The inhibitory activity of chloropropanoyl clinafloxacin was determined by routine drug sensitivity test.The perforation method and microbroth twofold dilution method was employed to determine the minimum inhibitory concentration(MIC)and minimum bactericidal concentration(MBC).The biofilm-forming abilities and growth rates of the seven strains exposed to sub-inhibitory concentrations of the drug were examined by crystalline violet staining.[Results]The fluoroquinolone derivative chloropropanoyl clinafloxacin showed the MIC≤10 mg/L and MBC≤48 mg/L against four Gram-negative strains and was sensitive to three Gram-positive strains(MIC≤10 mg/L and MBC≤10 mg/L).The biofilm formation and growth of the seven strains were significantly inhibited by chloropropanoyl clinafloxacin at the sub-inhibitory concentrations,which indicated that chloropropanoyl clinafloxacin had good antibacterial activity at sub-inhibitory concentrations.[Conclusion]Chloropropanoyl clinafloxacin can be used as an antibacterial agent and provides a basis for the development of new agents or drugs targeting biofilm for the treatment of bacterial infections.