Siriyong Thanyaluck, Chusri Sasitorn, Srimanote Potjanee, Tipmanee Varomyalin, Voravuthikunchai Supayang Piyawan
1 Department of Microbiology and Excellence Research Laboratory on Natural Products, Faculty of Science and Natural Product Research Center of Excellence, Prince of Songkla University , Hat Yai, Thailand .
2 Faculty of Traditional Thai Medicine and Excellence Research Laboratory on Natural Products, Faculty of Science and Natural Product Research Center of Excellence, Prince of Songkla University , Hat Yai, Thailand .
Microb Drug Resist. 2016 Jun;22(4):273-82. doi: 10.1089/mdr.2015.0194. Epub 2016 Jan 8.
Emergence and spread of antibiotic-resistant Acinetobacter baumannii have become a major public health concern. This study was designed to investigate the efficacy of Holarrhena antidysenterica extract and its major steroidal alkaloid conessine as resistance-modifying agents (RMAs) on the susceptibility of A. baumannii to novobiocin and rifampicin. A significant synergistic activity of both the extract and conessine in combination with either novobiocin or rifampicin with fractional inhibitory concentration index ≤0.5 was demonstrated. Fluorescent dyes and different efflux pump inhibitors were used to further investigate the synergism. Increase in the uptake of 1-N-phenylnaphthylamine in the bacterial cells treated with the extract and conessine was not observed indicating that both substances did not act as permeabilizers. With regard to efflux pump inhibition, no accumulation in ethidium bromide (EtBr) was noticed suggesting that the AdeABC pump was not involved. In contrast, accumulation in Pyronin Y was significantly increased (p < 0.05) demonstrating that the synergism was due to interference with the AdeIJK pump. Study on frequencies of the spontaneous mutational resistance to the extract in combination with antibiotics demonstrated attenuation in drug-resistant organisms. Thus, H. antidysenterica extract and conessine as RMAs may offer a combinatory therapy to restore antibiotic susceptibility in the extensively drug-resistant A. baumannii.
耐抗生素鲍曼不动杆菌的出现和传播已成为一个主要的公共卫生问题。本研究旨在调查止泻木提取物及其主要甾体生物碱康丝碱作为耐药性修饰剂（RMAs）对鲍曼不动杆菌对新生霉素和利福平敏感性的影响。结果表明，提取物和康丝碱与新生霉素或利福平联合使用时具有显著的协同活性，分数抑制浓度指数≤0.5。使用荧光染料和不同的外排泵抑制剂进一步研究协同作用。在用提取物和康丝碱处理的细菌细胞中未观察到1-N-苯基萘胺摄取增加，表明这两种物质均未起到通透剂的作用。关于外排泵抑制，未观察到溴化乙锭（EtBr）的积累，提示AdeABC泵未参与其中。相反，派洛宁Y中的积累显著增加（p<0.05），表明协同作用是由于对AdeIJK泵的干扰。对提取物与抗生素联合使用时自发突变耐药频率的研究表明，耐药菌有所减少。因此，止泻木提取物和康丝碱作为耐药性修饰剂可能为恢复广泛耐药鲍曼不动杆菌的抗生素敏感性提供联合治疗。
