RT Journal Article
SR Electronic
T1 Synergistic Interaction Between Proton Pump Inhibitors and Resistance Modifiers: Promoting Effects of Antibiotics and Plasmid Curing
JF In Vivo
JO In Vivo
FD International Institute of Anticancer Research
SP 367
OP 372
VO 20
IS 3
A1 WOLFART, KRISTINA
A1 SPENGLER, GABRIELLA
A1 KAWASE, MASAMI
A1 MOTOHASHI, NOBORU
A1 MOLNÁR, JOSEPH
A1 VIVEIROS, MIGUEL
A1 AMARAL, LEONARD
YR 2006
UL http://iv.iiarjournals.org/content/20/3/367.abstract
AB 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. Copyright © 2006 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved