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Fluorinated Beta-diketo Phosphorus Ylides Are Novel Efflux Pump Inhibitors in Bacteria.
In Vivo. 2016 11-12; 30(6):813-817.V

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.

Authors+Show Affiliations

Department of Medical Microbiology and Immunobiology, Faculty of Medicine, University of Szeged, Szeged, Hungary.Department of Medical Microbiology and Immunobiology, Faculty of Medicine, University of Szeged, Szeged, Hungary.Faculty of Pharmaceutical Sciences, Matsuyama University, Matsuyamas, Japan.Faculty of Pharmaceutical Sciences, Matsuyama University, Matsuyamas, Japan.Faculty of Pharmaceutical Sciences, Matsuyama University, Matsuyamas, Japan.Department of Medical Microbiology and Immunobiology, Faculty of Medicine, University of Szeged, Szeged, Hungary.Department of Medical Microbiology and Immunobiology, Faculty of Medicine, University of Szeged, Szeged, Hungary spengler.gabriella@med.u-szeged.hu.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27815466

Citation

Kincses, Annamária, et al. "Fluorinated Beta-diketo Phosphorus Ylides Are Novel Efflux Pump Inhibitors in Bacteria." In Vivo (Athens, Greece), vol. 30, no. 6, 2016, pp. 813-817.
Kincses A, Szabó ÁM, Saijo R, et al. Fluorinated Beta-diketo Phosphorus Ylides Are Novel Efflux Pump Inhibitors in Bacteria. In Vivo. 2016;30(6):813-817.
Kincses, A., Szabó, Á. M., Saijo, R., Watanabe, G., Kawase, M., Molnár, J., & Spengler, G. (2016). Fluorinated Beta-diketo Phosphorus Ylides Are Novel Efflux Pump Inhibitors in Bacteria. In Vivo (Athens, Greece), 30(6), 813-817.
Kincses A, et al. Fluorinated Beta-diketo Phosphorus Ylides Are Novel Efflux Pump Inhibitors in Bacteria. In Vivo. 2016;30(6):813-817. PubMed PMID: 27815466.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Fluorinated Beta-diketo Phosphorus Ylides Are Novel Efflux Pump Inhibitors in Bacteria. AU - Kincses,Annamária, AU - Szabó,Ágnes Míra, AU - Saijo,Ryosuke, AU - Watanabe,Genki, AU - Kawase,Masami, AU - Molnár,Joseph, AU - Spengler,Gabriella, PY - 2016/07/22/received PY - 2016/09/05/accepted PY - 2016/11/6/entrez PY - 2016/11/7/pubmed PY - 2018/1/30/medline KW - Phosphorus ylides KW - bacterial AcrAB-TolC KW - efflux pump KW - multidrug resistance KW - quorum sensing SP - 813 EP - 817 JF - In vivo (Athens, Greece) JO - In Vivo VL - 30 IS - 6 N2 - 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. SN - 1791-7549 UR - https://www.unboundmedicine.com/medline/citation/27815466/Fluorinated_Beta_diketo_Phosphorus_Ylides_Are_Novel_Efflux_Pump_Inhibitors_in_Bacteria_ L2 - http://iv.iiarjournals.org/cgi/pmidlookup?view=long&pmid=27815466 DB - PRIME DP - Unbound Medicine ER -