Fluorinated beta-diketo phosphorus ylides are novel efflux pump inhibitors in bacteria

Annamária Kincses, Ágnes Míra Szabó, Ryosuke Saijo, Genki Watanabe, Masami Kawase, J. Molnár, G. Spengler

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Background: One of the most important resistance mechanisms in bacteria is the increased expression of multidrug efflux pumps. To combat efflux-related resistance, the development of new efflux pump inhibitors is essential. Materials and Methods: Ten phosphorus ylides were compared based on their MDR-reverting activity in multidrug efflux pump system consisting of the subunits acridine-resistance proteins A and B (AcrA and AcrB) and the multidrug efflux pump outer membrane factor TolC (TolC) of Escherichia coli K-12 AG100 strain and its AcrAB-TolC-deleted strain. Efflux inhibition was assessed by real-time fluorimetry and the inhibition of quorum sensing (QS) was also investigated. The relative gene expression of efflux QS genes was determined by real-time reverse transcriptase quantitative polymerase chain reaction. Results: The most potent derivative was Ph3P=C(COC2F5)CHO and its effect was more pronounced on the AcrAB-TolC-expressing E. coli strain, furthermore the most active compounds, Ph3P=C(COCF3)OMe, Ph3P=C(COC2F5)CHO and Ph3P=C(COCF3)COMe, reduced the expression of efflux pump and QS genes. Conclusion: Phosphorus ylides might be valuable EPI compounds to reverse efflux related MDR in bacteria.

Original languageEnglish
Pages (from-to)813-817
Number of pages5
JournalIn Vivo
Volume30
Issue number6
DOIs
Publication statusPublished - Nov 1 2016

Fingerprint

Quorum Sensing
Phosphorus
Bacteria
Pumps
Escherichia coli
Acridines
Fluorometry
Staphylococcal Protein A
Reverse Transcriptase Polymerase Chain Reaction
Genes
Real-Time Polymerase Chain Reaction
Polymerase chain reaction
RNA-Directed DNA Polymerase
Gene Expression
Membranes
Gene expression
Derivatives

Keywords

  • Bacterial AcrAB-TolC
  • Efflux pump
  • Multidrug resistance
  • Phosphorus ylides
  • Quorum sensing

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology

Cite this

Fluorinated beta-diketo phosphorus ylides are novel efflux pump inhibitors in bacteria. / Kincses, Annamária; Szabó, Ágnes Míra; Saijo, Ryosuke; Watanabe, Genki; Kawase, Masami; Molnár, J.; Spengler, G.

In: In Vivo, Vol. 30, No. 6, 01.11.2016, p. 813-817.

Research output: Contribution to journalArticle

Kincses, Annamária ; Szabó, Ágnes Míra ; Saijo, Ryosuke ; Watanabe, Genki ; Kawase, Masami ; Molnár, J. ; Spengler, G. / Fluorinated beta-diketo phosphorus ylides are novel efflux pump inhibitors in bacteria. In: In Vivo. 2016 ; Vol. 30, No. 6. pp. 813-817.
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