Synergistic interaction between proton pump inhibitors and resistance modifiers: promoting effects of antibiotics and plasmid curing

Kristina Wolfart, Gabriella Spengler, Masami Kawase, Noboru Motohashi, Joseph Molnŕ, Miguel Viveiros, Leonard Amaral

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)367-372
Number of pages6
JournalIn Vivo
VolumeVol. 20
Issue numbern.º 3
Publication statusPublished - May 2006

Keywords

  • Bacterial transporters
  • E. coli
  • Multidrug resistance
  • Plasmid curing
  • Proton pump
  • Resistance modifiers
  • Trifluoromethyl-ketones

UN Sustainable Development Goals (SDGs)

  • SDG 3 - Good Health and Well-Being

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