Patel Mohit B, Garrad Evan C, Stavri Ariel, Gokel Michael R, Negin Saeedeh, Meisel Joseph W, Cusumano Zachary, Gokel George W
Center for Nanoscience, University of Missouri-St. Louis, 1 University Blvd., St. Louis, MO 63121, USA; Department of Biology, University of Missouri-St. Louis, 1 University Blvd., St. Louis, MO 63121, USA.
Department of Biology, University of Missouri-St. Louis, 1 University Blvd., St. Louis, MO 63121, USA.
Bioorg Med Chem. 2016 Jun 15;24(12):2864-70. doi: 10.1016/j.bmc.2016.04.058. Epub 2016 Apr 27.
Hydraphiles are synthetic amphiphiles that form ion-conducting pores in liposomal membranes. These pores exhibit open-close behavior when studied by planar bilayer conductance techniques. In previous work, we showed that when co-administered with various antibiotics to the DH5α strain of Escherichia coli, they enhanced the drug's potency. We report here potency enhancements at low concentrations of hydraphiles for the structurally and mechanistically unrelated antibiotics erythromycin, kanamycin, rifampicin, and tetracycline against Gram negative E. coli (DH5α and K-12) and Pseudomonas aeruginosa, as well as Gram positive Bacillus subtilis. Earlier work suggested that potency increases correlated to ion transport function. The data presented here comport with the function of hydraphiles to enhance membrane permeability in addition to, or instead of, their known function as ion conductors.
亲水剂是一类合成两亲分子,可在脂质体膜中形成离子传导孔。当采用平面双层电导技术进行研究时,这些孔表现出开闭行为。在之前的工作中,我们发现,当与各种抗生素共同施用于大肠杆菌DH5α菌株时,亲水剂可增强药物的效力。我们在此报告,低浓度亲水剂可增强结构和作用机制各异的抗生素(红霉素、卡那霉素、利福平及四环素)对革兰氏阴性大肠杆菌(DH5α和K-12)、铜绿假单胞菌以及革兰氏阳性枯草芽孢杆菌的效力。早期研究表明,效力增强与离子转运功能相关。本文提供的数据表明,亲水剂除了具有已知的离子导体功能外,还可增强膜通透性,或者其增强膜通透性的功能可替代离子导体功能。