Contribution of AcrAB-ToIC to multidrug resistance in an Escherichia coli sequence type 131 isolate

Sabine Schuster*, Martina Vavra, Tobias Schweigger, John W A Rossen, Yasufumi Matsumura, Winfried V. Kern

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

14 Citations (Scopus)

Abstract

Drug efflux by resistance-nodulation-cell division (RND)-type transporters, such as AcrAB-ToIC of Escherichia can, 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-ToIC-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-ToIC and its homologues and new efflux inhibitors. (C) 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

Original languageEnglish
Pages (from-to)477-481
Number of pages5
JournalInternational journal of antimicrobial agents
Volume50
Issue number3
Early online date6-Jul-2017
DOIs
Publication statusPublished - Sep-2017

Keywords

  • AcrAB-ToIC
  • Multidrug resistance
  • E. coli ST131 clinical isolate
  • Efflux inactivation
  • EFFLUX PUMP ACRB
  • FLUOROQUINOLONE RESISTANCE
  • ANTIMICROBIAL RESISTANCE
  • IDENTIFICATION
  • MUTAGENESIS
  • MUTATIONS
  • RESIDUES

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