ABCB1 p.Asp457Arg
| Predicted by SNAP2: | A: D (75%), C: D (75%), E: D (71%), F: D (85%), G: D (85%), H: D (85%), I: D (85%), K: D (85%), L: D (85%), M: D (85%), N: D (63%), P: D (80%), Q: D (80%), R: D (85%), S: D (75%), T: D (80%), V: D (85%), W: D (75%), Y: D (85%), |
| Predicted by PROVEAN: | A: D, C: D, E: D, F: D, G: D, H: D, I: D, K: D, L: D, M: D, N: D, P: D, Q: D, R: D, S: D, T: D, V: D, W: D, Y: D, |
[switch to compact view]
Comments [show]
None has been submitted yet.
[hide] The third-generation P-glycoprotein inhibitor tari... J Antimicrob Chemother. 2011 Apr;66(4):834-9. Epub 2011 Jan 19. Leitner I, Nemeth J, Feurstein T, Abrahim A, Matzneller P, Lagler H, Erker T, Langer O, Zeitlinger M
The third-generation P-glycoprotein inhibitor tariquidar may overcome bacterial multidrug resistance by increasing intracellular drug concentration.
J Antimicrob Chemother. 2011 Apr;66(4):834-9. Epub 2011 Jan 19., [PMID:21393173]
Abstract [show]
OBJECTIVES: The use of efflux pump inhibitors may be a powerful strategy to overcome transporter-mediated bacterial multidrug resistance. In the present study, we set out to investigate the potency of tariquidar, a third-generation P-glycoprotein inhibitor in clinical development, for overcoming bacterial resistance towards ciprofloxacin. METHODS: Staphylococcus aureus 29213 (SA29213) and S. aureus 1199B (SA1199B), which overexpresses the multidrug transporter NorA, as well as Pseudomonas aeruginosa 27853 and Stenotrophomonas maltophilia BAA-85, which expresses SmeDEF, were exposed to ciprofloxacin in the presence and absence of tariquidar or, for comparative reasons, elacridar. Activity of both P-glycoprotein inhibitors was evaluated by determination of MICs and time-kill curves, and by quantification of uptake of ciprofloxacin into bacterial cells. RESULTS: Activity of tariquidar and elacridar was comparable for S. aureus strains, and both dose-dependently increased susceptibility towards ciprofloxacin. Highest effects were observed for SA1199B, where the addition of tariquidar resulted in a 10-fold reduction of the ciprofloxacin MIC, while no effect was observed for P. aeruginosa. For S. maltophilia, elacridar but not tariquidar improved susceptibility. Uptake of [14C]ciprofloxacin and modification of susceptibility showed significant correlations (r=0.89, P<0.0001). Tariquidar had no intrinsic activity against any strain tested. CONCLUSIONS: We conclude that tariquidar has potent inhibitory effect against certain bacterial efflux pumps in vitro. Their high activity at clinically achievable concentrations might yield this class of drugs promising for future applications in infectious diseases.
Comments [show]
None has been submitted yet.
No. Sentence Comment
20 S. aureus 1199B (SA1199B), which overexpresses the major S. aureus multidrug transporter NorA, was generously provided by the Centre for Pharmacognosy and Phytotherapy, University of London.3 S. maltophilia ATCC BAA-85 (also described as D457R) expresses an efflux-mediated MDR system (SmeDEF) against a range of antibacterials, including quinolones.19,20 Antibiotics, chemicals and growth media Mueller-Hinton broth (MHB; Merck, Germany) was adjusted with cations to concentrations of 25 mg/L calcium and 12.5 mg/L magnesium, according to the CLSI.
X
ABCB1 p.Asp457Arg 21393173:20:238
status: NEW