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Contribution of AcrAB-TolC to multidrug resistance in an Escherichia coli sequence type 131 isolate.
Int J Antimicrob Agents 2017; 50(3):477-481IJ

Abstract

Drug efflux by resistance-nodulation-cell division (RND)-type transporters, such as AcrAB-TolC of Escherichia coli, is an important resistance mechanism in Gram-negative bacteria; however, its contribution to multidrug resistance (MDR) in clinical isolates is poorly defined. We inactivated acrB of a sequence type 131 E. coli human isolate that showed high-level MDR, but had no mutations within the known efflux-associated local or global regulators. The resistance profile of the acrB deletion mutant revealed significantly increased susceptibility to drugs from seven antibiotic classes, including agents usually inactive against Gram-negative bacteria, notably the new oxazolidinone, tedizolid (512-fold enhanced susceptibility). AcrB deficiency reduced, but did not abolish, the efflux of dyes, which indicates the activity of at least one more efflux transporter. The findings demonstrate the efficacy of AcrAB-TolC-mediated broad-spectrum drug efflux, including agents primarily developed for Gram-positive pathogens, in a clinical isolate representative of a globally-emerging lineage. The results illustrate the need to develop molecules modified to impede their transport by AcrAB-TolC and its homologues and new efflux inhibitors.

Authors+Show Affiliations

Division of Infectious Diseases, Department of Medicine, University Hospital and Medical Center, Freiburg, Germany. Electronic address: sabine.schuster@uniklinik-freiburg.de.Division of Infectious Diseases, Department of Medicine, University Hospital and Medical Center, Freiburg, Germany.Division of Infectious Diseases, Department of Medicine, University Hospital and Medical Center, Freiburg, Germany.Department of Medical Microbiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.Department of Clinical Laboratory Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.Division of Infectious Diseases, Department of Medicine, University Hospital and Medical Center, Freiburg, Germany; Albert-Ludwigs-University Faculty of Medicine, Freiburg, Germany.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28689875

Citation

Schuster, Sabine, et al. "Contribution of AcrAB-TolC to Multidrug Resistance in an Escherichia Coli Sequence Type 131 Isolate." International Journal of Antimicrobial Agents, vol. 50, no. 3, 2017, pp. 477-481.
Schuster S, Vavra M, Schweigger TM, et al. Contribution of AcrAB-TolC to multidrug resistance in an Escherichia coli sequence type 131 isolate. Int J Antimicrob Agents. 2017;50(3):477-481.
Schuster, S., Vavra, M., Schweigger, T. M., Rossen, J. W. A., Matsumura, Y., & Kern, W. V. (2017). Contribution of AcrAB-TolC to multidrug resistance in an Escherichia coli sequence type 131 isolate. International Journal of Antimicrobial Agents, 50(3), pp. 477-481. doi:10.1016/j.ijantimicag.2017.03.023.
Schuster S, et al. Contribution of AcrAB-TolC to Multidrug Resistance in an Escherichia Coli Sequence Type 131 Isolate. Int J Antimicrob Agents. 2017;50(3):477-481. PubMed PMID: 28689875.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Contribution of AcrAB-TolC to multidrug resistance in an Escherichia coli sequence type 131 isolate. AU - Schuster,Sabine, AU - Vavra,Martina, AU - Schweigger,Tobias M, AU - Rossen,John W A, AU - Matsumura,Yasufumi, AU - Kern,Winfried V, Y1 - 2017/07/06/ PY - 2016/12/06/received PY - 2017/03/15/revised PY - 2017/03/18/accepted PY - 2017/7/12/pubmed PY - 2018/5/9/medline PY - 2017/7/11/entrez KW - AcrAB-TolC KW - E. coli ST131 clinical isolate KW - Efflux inactivation KW - Multidrug resistance SP - 477 EP - 481 JF - International journal of antimicrobial agents JO - Int. J. Antimicrob. Agents VL - 50 IS - 3 N2 - Drug efflux by resistance-nodulation-cell division (RND)-type transporters, such as AcrAB-TolC of Escherichia coli, is an important resistance mechanism in Gram-negative bacteria; however, its contribution to multidrug resistance (MDR) in clinical isolates is poorly defined. We inactivated acrB of a sequence type 131 E. coli human isolate that showed high-level MDR, but had no mutations within the known efflux-associated local or global regulators. The resistance profile of the acrB deletion mutant revealed significantly increased susceptibility to drugs from seven antibiotic classes, including agents usually inactive against Gram-negative bacteria, notably the new oxazolidinone, tedizolid (512-fold enhanced susceptibility). AcrB deficiency reduced, but did not abolish, the efflux of dyes, which indicates the activity of at least one more efflux transporter. The findings demonstrate the efficacy of AcrAB-TolC-mediated broad-spectrum drug efflux, including agents primarily developed for Gram-positive pathogens, in a clinical isolate representative of a globally-emerging lineage. The results illustrate the need to develop molecules modified to impede their transport by AcrAB-TolC and its homologues and new efflux inhibitors. SN - 1872-7913 UR - https://www.unboundmedicine.com/medline/citation/28689875/Contribution_of_AcrAB_TolC_to_multidrug_resistance_in_an_Escherichia_coli_sequence_type_131_isolate_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0924-8579(17)30252-2 DB - PRIME DP - Unbound Medicine ER -