TY - JOUR
T1 - Synergistic interaction between proton pump inhibitors and resistance modifiers
T2 - promoting effects of antibiotics and plasmid curing
AU - Wolfart, Kristina
AU - Spengler, Gabriella
AU - Kawase, Masami
AU - Motohashi, Noboru
AU - Molnŕ, Joseph
AU - Viveiros, Miguel
AU - Amaral, Leonard
PY - 2006/5
Y1 - 2006/5
N2 - A proton pump-deleted mutant E. coli, AGI00 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 plasmds 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.
AB - A proton pump-deleted mutant E. coli, AGI00 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 plasmds 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.
KW - Bacterial transporters
KW - E. coli
KW - Multidrug resistance
KW - Plasmid curing
KW - Proton pump
KW - Resistance modifiers
KW - Trifluoromethyl-ketones
UR - http://www.scopus.com/inward/record.url?scp=33646849578&partnerID=8YFLogxK
UR - http://iv.iiarjournals.org/content/20/3/367.long
M3 - Article
C2 - 16724672
AN - SCOPUS:33646849578
SN - 0258-851X
VL - Vol. 20
SP - 367
EP - 372
JO - In Vivo
JF - In Vivo
IS - n.º 3
ER -