Division of Crop Protection/Division of Crop Utilization, Central Tuber Crops Research Institute, Sreekariyam, Thiruvananthapuram 695017, India.
World J Microbiol Biotechnol. 2012 Nov;28(11):3143-50. doi: 10.1007/s11274-012-1124-0. Epub 2012 Jul 11.
The synergistic antibacterial activity of two stilbenes [3,4',5-trihydroxystilbene (1) and 3,5-dihydroxy-4-isopropylstilbene(2)] purified from a Bacillus sp. N strain associated with entomopathogenic nematode Rhabditis (Oscheius) in combination with ciprofloxacin and cefotaxime was investigated. The activity of the stilbenes and standard antibiotics on bacteria were determined using the macrodilution method. The minimum inhibitory concentration and minimum bactericidal concentration of the stilbenes was compared with that of the standard antibiotics. The antibacterial activities of stilbenes against pathogenic bacteria were assessed using the checkerboard and time-kill methods to evaluate the synergistic effects of stilbenes in treatment with ciprofloxacin or cefotaxime. The results of the present study showed that the combination effects of both stilbenes with ciprofloxacin were synergistic (FIC index <0.5). Whereas stilbene 2 with cefotaxime recorded additive. Furthermore, time-kill study showed that the growth of the tested bacteria was completely attenuated with 12-24 h of treatment with 50:50 ratios of stilbenes and antibiotics. These results suggest that stilbenes combined with antibiotics may be microbiologically beneficial and not antagonistic. These findings have potential implications in delaying the development of resistance as the antibacterial effect is achieved with lower concentrations of both drugs (antibiotics and stilbenes). The in vitro synergistic activity of stilbenes and antibiotics against bacteria is reported here for the first time.
两种芪类化合物（3,4',5-三羟基芪（1）和 3,5-二羟基-4-异丙基芪（2））从与昆虫病原线虫共生的芽孢杆菌 N 菌株中分离出来，与环丙沙星和头孢噻肟联合使用时具有协同抗菌活性。使用大稀释法测定芪类化合物和标准抗生素对细菌的活性。比较了芪类化合物和标准抗生素的最低抑菌浓度和最低杀菌浓度。使用棋盘和时间杀伤法评估芪类化合物对致病菌的抗菌活性，以评估芪类化合物与环丙沙星或头孢噻肟联合治疗的协同作用。本研究结果表明，两种芪类化合物与环丙沙星的组合效果均具有协同作用（FIC 指数<0.5）。而芪 2 与头孢噻肟的组合效果为相加。此外，时间杀伤研究表明，用 50:50 的芪类化合物和抗生素比例处理 12-24 小时后，测试细菌的生长完全受到抑制。这些结果表明，芪类化合物与抗生素联合使用可能具有微生物有益作用，而不是拮抗作用。由于使用较低浓度的两种药物（抗生素和芪类化合物）即可达到抗菌效果，因此这些发现可能对延缓耐药性的发展具有重要意义。这是首次报道芪类化合物和抗生素对细菌的体外协同活性。
