Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Kita, Okayama, Japan.
J Microbiol Methods. 2012 Dec;91(3):497-500. doi: 10.1016/j.mimet.2012.09.033. Epub 2012 Oct 7.
We introduced a new assay system, combining tyrocidine A and a K(+)-selective electrode, to evaluate the bacterial outer membrane-permeabilizing ability of drugs. Tyrocidine A, in the presence of an outer membrane permeabilizer, increased the permeability to K(+) of the cytoplasmic membrane of Escherichia coli, because this antibiotic could markedly increase the permeability of phospholipid layers constituting the cytoplasmic membrane, while it acted weakly on the outer membrane. Hence, the novel function of agents increasing the permeability of the outer membrane could be examined directly by monitoring the tyrocidine A-induced leakage of K(+) from the bacterial cytoplasm using a K(+)-selective electrode. We found that antiprotozoal diamidines, such as diminazene, pentamidine, and 4',6-diamidino-2-phenylindole (DAPI), can increase the permeability of the bacterial outer membrane and appropriate lipophilicity is important for diamidines to permeabilize the outer membrane.
我们引入了一种新的测定系统，结合短杆菌肽 A 和 K(+)选择性电极，来评估药物对细菌外膜通透性的改变作用。短杆菌肽 A 在存在外膜通透剂的情况下，增加了大肠杆菌细胞质膜对 K(+)的通透性，因为这种抗生素可以显著增加构成细胞质膜的磷脂层的通透性，而对外膜的作用较弱。因此，通过使用 K(+)选择性电极监测短杆菌肽 A 诱导的细菌细胞质中 K(+)的泄漏，可以直接检测增加外膜通透性的试剂的新功能。我们发现抗原生动物的二脒类化合物，如苯脒、戊二脒和 4',6-二脒基-2-苯基吲哚（DAPI），可以增加细菌外膜的通透性，并且适当的亲脂性对于二脒类化合物通透外膜是重要的。
