Fluorinated Beta-diketo Phosphorus Ylides Are Novel Efflux Pump Inhibitors in Bacteria
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 MD...
Elmentve itt :
| Szerzők: | |
|---|---|
| Dokumentumtípus: | Cikk |
| Megjelent: |
2016
|
| Sorozat: | IN VIVO
30 No. 6 |
| doi: | 10.21873/invivo.10999 |
| mtmt: | 3135011 |
| Online Access: | http://publicatio.bibl.u-szeged.hu/10423 |
| Tartalmi kivonat: | 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. |
|---|---|
| Terjedelem/Fizikai jellemzők: | 813-817 |
| ISSN: | 0258-851X |