Wolfart Kristina, Spengler Gabriella, Kawase Masami, Motohashi Noboru, Molnár Joseph, Viveiros Miguel, Amaral Leonard
Department of Medical Microbiology, University of Szeged, 6720 Szeged, Dóm tér 10, Hungary.
In Vivo. 2006 May-Jun;20(3):367-72.
A proton pump-deleted mutant E. coli, AG100 A, had greater sensitivity to ampicillin, tetracycline and erythromycin than the wild-type parent E. coli AG100 containing the proton pump. This antibiotic sensitivity was further increased by resistance modifiers such as the Ca2+ channel blocker (+/-) verapamil (VP) and the calmodulin antagonist promethazine (PMZ). Whereas the newly-synthesized trifluoromethyl-ketone (TF) enhanced the activity of these antibiotics against the wild-type strain, it did not enhance the activity of ampicillin against the proton pump-deleted mutant. These results suggested that TF14 had an inhibitory effect on the proton pump. Elimination of plasmids from another strain of E. coli, K12, was promoted by PMZ and 9-amino-acridine (9-AA), but not by TF14 alone. However, combinations of TF14 with either PMZ or 9-AA enhanced the plasmid elimination capacity of the latter compounds. The combination of TF14, PMZ and VP proved that the Ca2+ channel blocker was not effective by itself These results collectively suggest that TF14 inhibited the proton pump of E. coli and that it was this pump which, when inhibited by TF14, allowed more PMZ to reach its plasmid elimination target.
一种缺失质子泵的大肠杆菌突变体AG100 A，对氨苄青霉素、四环素和红霉素的敏感性比含有质子泵的野生型亲代大肠杆菌AG100更高。这种抗生素敏感性通过诸如Ca2+通道阻滞剂（±）维拉帕米（VP）和钙调蛋白拮抗剂异丙嗪（PMZ）等抗性修饰剂进一步增强。而新合成的三氟甲基酮（TF）增强了这些抗生素对野生型菌株的活性，但它并未增强氨苄青霉素对缺失质子泵突变体的活性。这些结果表明TF14对质子泵有抑制作用。PMZ和9-氨基吖啶（9-AA）可促进从另一株大肠杆菌K12中消除质粒，但单独使用TF14则不能。然而，TF14与PMZ或9-AA的组合增强了后一种化合物的质粒消除能力。TF14、PMZ和VP的组合证明Ca2+通道阻滞剂本身无效。这些结果共同表明TF14抑制了大肠杆菌的质子泵，并且正是这种泵在被TF14抑制时，使得更多的PMZ能够到达其质粒消除靶点。
