This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Michot, J.-M.
Right arrow Articles by Van Bambeke, F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Michot, J.-M.
Right arrow Articles by Van Bambeke, F.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, May 2006, p. 1689-1695, Vol. 50, No. 5
0066-4804/06/$08.00+0     doi:10.1128/AAC.50.5.1689-1695.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Cellular Accumulation and Activity of Quinolones in Ciprofloxacin-Resistant J774 Macrophages

Jean-Michel Michot,{dagger} Marie F. Heremans,{dagger} Nancy E. Caceres, Marie-Paule Mingeot-Leclercq, Paul M. Tulkens, and Françoise Van Bambeke*

Unité de Pharmacologie Cellulaire et Moléculaire, Université Catholique de Louvain, Brussels, Belgium

Received 10 November 2005/ Returned for modification 29 January 2006/ Accepted 13 February 2006

Ciprofloxacin is the substrate for a multidrug resistance-related protein (MRP)-like multidrug transporter in J774 mouse macrophages, which also modestly affects levofloxacin but only marginally affects garenoxacin and moxifloxacin (J.-M. Michot et al., Antimicrob. Agents Chemother. 49:2429-2437, 2005). Two clones of ciprofloxacin-resistant cells were obtained by a stepwise increase in drug concentration (from 34 to 51 to 68 mg/liter) in the culture fluid. Compared to wild-type cells, ciprofloxacin-resistant cells showed (i) a markedly reduced ciprofloxacin accumulation (12% of control) and (ii) a two- to threefold lower sensitivity to the enhancing effect exerted by MRP-inhibitors (probenecid and MK571) on ciprofloxacin accumulation or by ciprofloxacin itself. ATP-depletion brought ciprofloxacin accumulation to similarly high levels in both wild-type and ciprofloxacin-resistant cells. Garenoxacin and moxifloxacin accumulation remained unaffected, and levofloxacin showed an intermediate behavior. DNA and protein synthesis were not impaired in ciprofloxacin-resistant cells for ciprofloxacin concentrations up to 100 mg/liter (~85 and 55% inhibition, respectively, in wild-type cells). In Listeria monocytogenes-infected ciprofloxacin-resistant cells, 12-fold higher extracellular concentrations of ciprofloxacin were needed to show a bacteriostatic effect in comparison with wild-type cells. The data suggest that the resistance mechanism is mediated by an overexpression and/or increased activity of the MRP-like ciprofloxacin transporter expressed at a basal level in wild-type J774 macrophages, which modulates both the intracellular pharmacokinetics and activity of ciprofloxacin.

* Corresponding author. Mailing address: Unité de Pharmacologie Cellulaire et Moléculaire, UCL 7370, avenue Mounier 73, 1200 Brussels, Belgium. Phone: 32 2 764 73 78. Fax: 32 2 764 73 73. E-mail: vanbambeke{at}facm.ucl.ac.be.

{dagger} J.-M.M. and M.F.H. contributed equally to this study.

Antimicrobial Agents and Chemotherapy, May 2006, p. 1689-1695, Vol. 50, No. 5
0066-4804/06/$08.00+0     doi:10.1128/AAC.50.5.1689-1695.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Lemaire, S., Van Bambeke, F., Appelbaum, P. C., Tulkens, P. M. (2009). Cellular pharmacokinetics and intracellular activity of torezolid (TR-700): studies with human macrophage (THP-1) and endothelial (HUVEC) cell lines. J Antimicrob Chemother 64: 1035-1043 [Abstract] [Full Text]  
  • Marquez, B., Caceres, N. E., Mingeot-Leclercq, M.-P., Tulkens, P. M., Van Bambeke, F. (2009). Identification of the Efflux Transporter of the Fluoroquinolone Antibiotic Ciprofloxacin in Murine Macrophages: Studies with Ciprofloxacin-Resistant Cells. Antimicrob. Agents Chemother. 53: 2410-2416 [Abstract] [Full Text]  
  • Lismond, A., Tulkens, P. M., Mingeot-Leclercq, M.-P., Courvalin, P., Van Bambeke, F. (2008). Cooperation between Prokaryotic (Lde) and Eukaryotic (MRP) Efflux Transporters in J774 Macrophages Infected with Listeria monocytogenes: Studies with Ciprofloxacin and Moxifloxacin. Antimicrob. Agents Chemother. 52: 3040-3046 [Abstract] [Full Text]  
  • Grayo, S., Lott-Desroches, M.-C., Dussurget, O., Respaud, R., Fontanet, A., Join-Lambert, O., Singlas, E., Le Monnier, A. (2008). Rapid Eradication of Listeria monocytogenes by Moxifloxacin in a Murine Model of Central Nervous System Listeriosis. Antimicrob. Agents Chemother. 52: 3210-3215 [Abstract] [Full Text]  
  • Grayo, S., Join-Lambert, O., Desroches, M. C., Le Monnier, A. (2008). Comparison of the In Vitro Efficacies of Moxifloxacin and Amoxicillin against Listeria monocytogenes. Antimicrob. Agents Chemother. 52: 1697-1702 [Abstract] [Full Text]  
  • Lemaire, S., Van Bambeke, F., Mingeot-Leclercq, M.-P., Tulkens, P. M. (2007). Modulation of the Cellular Accumulation and Intracellular Activity of Daptomycin towards Phagocytized Staphylococcus aureus by the P-Glycoprotein (MDR1) Efflux Transporter in Human THP-1 Macrophages and Madin-Darby Canine Kidney Cells. Antimicrob. Agents Chemother. 51: 2748-2757 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»