Previous Article | Next Article 
Antimicrobial Agents and Chemotherapy, March 2002, p. 808-812, Vol. 46, No. 3
0066-4804/02/$04.00+0 DOI: 10.1128/AAC.46.3.808-812.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.
Expression of Efflux Pump Gene pmrA in Fluoroquinolone-Resistant and -Susceptible Clinical Isolates of Streptococcus pneumoniae
Laura J. V. Piddock,* Maggie M. Johnson, S. Simjee,
and L. Pumbwe
Division of Immunity and Infection, University of Birmingham, Birmingham B15 2TT, United Kingdom
Received 7 May 2001/
Returned for modification 18 July 2001/
Accepted 11 December 2001
Thirty-four ciprofloxacin-resistant (MIC
2 µg/ml) and 12 ciprofloxacin-susceptible clinical isolates of Streptococcus pneumoniae were divided into four groups based upon susceptibility to norfloxacin and the effect of reserpine (20 µg/ml). The quinolone-resistance-determining regions of parC, parE, gyrA, and gyrB of all ciprofloxacin-resistant clinical isolates were sequenced, and the activities of eight other fluoroquinolones, acriflavine, ethidium bromide, chloramphenicol, and tetracycline in the presence and absence of reserpine were determined. Despite a marked effect of reserpine upon the activity of norfloxacin, there were only a few isolates for which the activity of another fluoroquinolone was enhanced by reserpine. For most isolates the MICs of acriflavine and ethidium bromide were lowered in the presence of reserpine despite the lack of effect of this efflux pump inhibitor on fluoroquinolone activity. The strains that were most resistant to the fluoroquinolones were predominantly those with mutations in three genes. Expression of the gene encoding the efflux pump PmrA was examined by Northern blotting (quantified by quantitative competitive reverse transcriptase PCR) and compared with that of S. pneumoniae R6 and R6N. Within each group there were isolates that had high-, medium-, and low-level expression of this gene; however, increased expression was not exclusively associated with those isolates with a phenotype suggestive of an efflux mutant. These data suggest that there is another reserpine-sensitive efflux pump in S. pneumoniae that extrudes ethidium bromide and acriflavine but not fluoroquinolones.
* Corresponding author. Mailing address: Division of Immunity and Infection, University of Birmingham, Birmingham B15 2TT, United Kingdom. Phone: 0121-414-6966. Fax: 0121-414-3454. E-mail: l.j.v.piddock{at}bham.ac.uk.
Present address: U.S. Food and Drug Administration, Center for Veterinary Medicine, Laurel, MD 20708.
Antimicrobial Agents and Chemotherapy, March 2002, p. 808-812, Vol. 46, No. 3
0066-4804/02/$04.00+0 DOI: 10.1128/AAC.46.3.808-812.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.
This article has been cited by other articles:
-
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]
-
Kumar, A., Khan, I. A., Koul, S., Koul, J. L., Taneja, S. C., Ali, I., Ali, F., Sharma, S., Mirza, Z. M., Kumar, M., Sangwan, P. L., Gupta, P., Thota, N., Qazi, G. N.
(2008). Novel structural analogues of piperine as inhibitors of the NorA efflux pump of Staphylococcus aureus. J Antimicrob Chemother
61: 1270-1276
[Abstract]
[Full Text]
-
Garvey, M. I., Piddock, L. J. V.
(2008). The Efflux Pump Inhibitor Reserpine Selects Multidrug-Resistant Streptococcus pneumoniae Strains That Overexpress the ABC Transporters PatA and PatB. Antimicrob. Agents Chemother.
52: 1677-1685
[Abstract]
[Full Text]
-
Avrain, L., Garvey, M., Mesaros, N., Glupczynski, Y., Mingeot-Leclercq, M.-P., Piddock, L. J. V., Tulkens, P. M., Vanhoof, R., Van Bambeke, F.
(2007). Selection of quinolone resistance in Streptococcus pneumoniae exposed in vitro to subinhibitory drug concentrations. J Antimicrob Chemother
60: 965-972
[Abstract]
[Full Text]
-
Shin, J. H., Jung, H. J., Kim, H. R., Jeong, J., Jeong, S. H., Kim, S., Lee, E. Y., Lee, J. N., Chang, C. L.
(2007). Prevalence, Characteristics, and Molecular Epidemiology of Macrolide and Fluoroquinolone Resistance in Clinical Isolates of Streptococcus pneumoniae at Five Tertiary-Care Hospitals in Korea. Antimicrob. Agents Chemother.
51: 2625-2627
[Abstract]
[Full Text]
-
Vidaillac, C., Guillon, J., Arpin, C., Forfar-Bares, I., Ba, B. B., Grellet, J., Moreau, S., Caignard, D.-H., Jarry, C., Quentin, C.
(2007). Synthesis of Omeprazole Analogues and Evaluation of These as Potential Inhibitors of the Multidrug Efflux Pump NorA of Staphylococcus aureus. Antimicrob. Agents Chemother.
51: 831-838
[Abstract]
[Full Text]
-
Oyamada, Y., Ito, H., Inoue, M., Yamagishi, J.-i.
(2006). Topoisomerase mutations and efflux are associated with fluoroquinolone resistance in Enterococcus faecalis.. J Med Microbiol
55: 1395-1401
[Abstract]
[Full Text]
-
Piddock, L. J. V.
(2006). Clinically Relevant Chromosomally Encoded Multidrug Resistance Efflux Pumps in Bacteria. Clin. Microbiol. Rev.
19: 382-402
[Abstract]
[Full Text]
-
Leavis, H. L., Willems, R. J. L., Top, J., Bonten, M. J. M.
(2006). High-Level Ciprofloxacin Resistance from Point Mutations in gyrA and parC Confined to Global Hospital-Adapted Clonal Lineage CC17 of Enterococcus faecium.. J. Clin. Microbiol.
44: 1059-1064
[Abstract]
[Full Text]
-
Marrer, E., Schad, K., Satoh, A. T., Page, M. G. P., Johnson, M. M., Piddock, L. J. V.
(2006). Involvement of the Putative ATP-Dependent Efflux Proteins PatA and PatB in Fluoroquinolone Resistance of a Multidrug-Resistant Mutant of Streptococcus pneumoniae. Antimicrob. Agents Chemother.
50: 685-693
[Abstract]
[Full Text]
-
Marrer, E., Satoh, A. T., Johnson, M. M., Piddock, L. J. V., Page, M. G. P.
(2006). Global Transcriptome Analysis of the Responses of a Fluoroquinolone-Resistant Streptococcus pneumoniae Mutant and Its Parent to Ciprofloxacin. Antimicrob. Agents Chemother.
50: 269-278
[Abstract]
[Full Text]
-
Wierzbowski, A. K., Boyd, D., Mulvey, M., Hoban, D. J., Zhanel, G. G.
(2005). Expression of the mef(E) Gene Encoding the Macrolide Efflux Pump Protein Increases in Streptococcus pneumoniae with Increasing Resistance to Macrolides. Antimicrob. Agents Chemother.
49: 4635-4640
[Abstract]
[Full Text]
-
Robertson, G. T., Doyle, T. B., Lynch, A. S.
(2005). Use of an Efflux-Deficient Streptococcus pneumoniae Strain Panel To Identify ABC-Class Multidrug Transporters Involved in Intrinsic Resistance to Antimicrobial Agents. Antimicrob. Agents Chemother.
49: 4781-4783
[Abstract]
[Full Text]
-
Smith-Adam, H. J., Nichol, K. A., Hoban, D. J., Zhanel, G. G.
(2005). Stability of Fluoroquinolone Resistance in Streptococcus pneumoniae Clinical Isolates and Laboratory-Derived Mutants. Antimicrob. Agents Chemother.
49: 846-848
[Abstract]
[Full Text]
-
Raherison, S., Gonzalez, P., Renaudin, H., Charron, A., Bebear, C., Bebear, C. M.
(2005). Increased Expression of Two Multidrug Transporter-Like Genes Is Associated with Ethidium Bromide and Ciprofloxacin Resistance in Mycoplasma hominis. Antimicrob. Agents Chemother.
49: 421-424
[Abstract]
[Full Text]
-
Smith, H. J., Noreddin, A. M., Siemens, C. G., Schurek, K. N., Greisman, J., Hoban, C. J., Hoban, D. J., Zhanel, G. G.
(2004). Designing Fluoroquinolone Breakpoints for Streptococcus pneumoniae by Using Genetics instead of Pharmacokinetics-Pharmacodynamics. Antimicrob. Agents Chemother.
48: 3630-3635
[Abstract]
[Full Text]
-
Huda, N., Lee, E.-W., Chen, J., Morita, Y., Kuroda, T., Mizushima, T., Tsuchiya, T.
(2003). Molecular Cloning and Characterization of an ABC Multidrug Efflux Pump, VcaM, in Non-O1 Vibrio cholerae. Antimicrob. Agents Chemother.
47: 2413-2417
[Abstract]
[Full Text]
Copyright © 2002 by the American Society for Microbiology. All rights reserved.