Tags

Type your tag names separated by a space and hit enter

Kinetic parameters of efflux of penicillins by the multidrug efflux transporter AcrAB-TolC of Escherichia coli.
Antimicrob Agents Chemother. 2010 May; 54(5):1800-6.AA

Abstract

The multidrug efflux transporter AcrAB-TolC is known to pump out a diverse range of antibiotics, including beta-lactams. However, the kinetic constants of the efflux process, needed for the quantitative understanding of resistance, were not available until those accompanying the efflux of some cephalosporins were recently determined by combining efflux with the hydrolysis of drugs by the periplasmic beta-lactamase. In the present study we extended this approach to the study of a wide range of penicillins, from ampicillin and penicillin V to ureidopenicillins and isoxazolylpenicillins, by combining efflux with hydrolysis with the OXA-7 penicillinase. We found that the penicillins had a much stronger apparent affinity to AcrB and higher maximum rates of efflux than the cephalosporins. All penicillins showed strong positive cooperativity kinetics for export. The kinetic constants obtained were validated, as the MICs theoretically predicted on the basis of efflux and hydrolysis kinetics were remarkably similar to the observed MICs (except for the isoxazolylpenicillins). Surprisingly, however, the efflux kinetics of cloxacillin, for example, whose MIC decreased 512-fold in Escherichia coli upon the genetic deletion of the acrB gene, were quite similar to those of ampicillin, whose MIC decreased only 2-fold with the same treatment. Analysis of this phenomenon showed that the extensive decrease in the MIC for the acrB mutant is primarily due to the low permeation of the drug and that comparison of the MICs between the parent and the acrB strains is a very poor measure of the ability of AcrB to pump a drug out.

Authors+Show Affiliations

Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720-3202, USA.No affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

20160052

Citation

Lim, Siew Ping, and Hiroshi Nikaido. "Kinetic Parameters of Efflux of Penicillins By the Multidrug Efflux Transporter AcrAB-TolC of Escherichia Coli." Antimicrobial Agents and Chemotherapy, vol. 54, no. 5, 2010, pp. 1800-6.
Lim SP, Nikaido H. Kinetic parameters of efflux of penicillins by the multidrug efflux transporter AcrAB-TolC of Escherichia coli. Antimicrob Agents Chemother. 2010;54(5):1800-6.
Lim, S. P., & Nikaido, H. (2010). Kinetic parameters of efflux of penicillins by the multidrug efflux transporter AcrAB-TolC of Escherichia coli. Antimicrobial Agents and Chemotherapy, 54(5), 1800-6. https://doi.org/10.1128/AAC.01714-09
Lim SP, Nikaido H. Kinetic Parameters of Efflux of Penicillins By the Multidrug Efflux Transporter AcrAB-TolC of Escherichia Coli. Antimicrob Agents Chemother. 2010;54(5):1800-6. PubMed PMID: 20160052.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Kinetic parameters of efflux of penicillins by the multidrug efflux transporter AcrAB-TolC of Escherichia coli. AU - Lim,Siew Ping, AU - Nikaido,Hiroshi, Y1 - 2010/02/16/ PY - 2010/2/18/entrez PY - 2010/2/18/pubmed PY - 2010/7/23/medline SP - 1800 EP - 6 JF - Antimicrobial agents and chemotherapy JO - Antimicrob. Agents Chemother. VL - 54 IS - 5 N2 - The multidrug efflux transporter AcrAB-TolC is known to pump out a diverse range of antibiotics, including beta-lactams. However, the kinetic constants of the efflux process, needed for the quantitative understanding of resistance, were not available until those accompanying the efflux of some cephalosporins were recently determined by combining efflux with the hydrolysis of drugs by the periplasmic beta-lactamase. In the present study we extended this approach to the study of a wide range of penicillins, from ampicillin and penicillin V to ureidopenicillins and isoxazolylpenicillins, by combining efflux with hydrolysis with the OXA-7 penicillinase. We found that the penicillins had a much stronger apparent affinity to AcrB and higher maximum rates of efflux than the cephalosporins. All penicillins showed strong positive cooperativity kinetics for export. The kinetic constants obtained were validated, as the MICs theoretically predicted on the basis of efflux and hydrolysis kinetics were remarkably similar to the observed MICs (except for the isoxazolylpenicillins). Surprisingly, however, the efflux kinetics of cloxacillin, for example, whose MIC decreased 512-fold in Escherichia coli upon the genetic deletion of the acrB gene, were quite similar to those of ampicillin, whose MIC decreased only 2-fold with the same treatment. Analysis of this phenomenon showed that the extensive decrease in the MIC for the acrB mutant is primarily due to the low permeation of the drug and that comparison of the MICs between the parent and the acrB strains is a very poor measure of the ability of AcrB to pump a drug out. SN - 1098-6596 UR - https://www.unboundmedicine.com/medline/citation/20160052/Kinetic_parameters_of_efflux_of_penicillins_by_the_multidrug_efflux_transporter_AcrAB_TolC_of_Escherichia_coli_ L2 - http://aac.asm.org/cgi/pmidlookup?view=long&pmid=20160052 DB - PRIME DP - Unbound Medicine ER -