Proximal Binding Pocket Arg717 Substitutions in Escherichia coli AcrB Cause Clinically Relevant Divergencies in Resistance Profiles

Antimicrob Agents Chemother. 2022 Apr 19;66(4):e0239221. doi: 10.1128/aac.02392-21. Epub 2022 Mar 21.

Abstract

Recent mutations in RND efflux pumps in clinical strains have further increased multidrug resistance. We show that R717L and R717Q substitutions (found in azithromycin-resistant Salmonella enterica spp.) in the Escherichia coli efflux pump AcrB dramatically increase macrolide, as well as fluoroquinolone, resistance. On the other hand, cells became more susceptible to novobiocin and β-lactam cloxacillin. We urge the control of, and adjustments to, treatments with antibiotics and the need for novel antibiotics and efflux pump inhibitors.

Keywords: AcrB; RND; antimicrobial resistance; fluoroquinolones; macrolides; multidrug resistance.

MeSH terms

  • Anti-Bacterial Agents / chemistry
  • Azithromycin / pharmacology
  • Drug Resistance, Multiple, Bacterial / genetics
  • Escherichia coli Proteins* / genetics
  • Escherichia coli Proteins* / metabolism
  • Escherichia coli* / genetics
  • Escherichia coli* / metabolism
  • Multidrug Resistance-Associated Proteins / genetics
  • Multidrug Resistance-Associated Proteins / metabolism

Substances

  • AcrB protein, E coli
  • Anti-Bacterial Agents
  • Escherichia coli Proteins
  • Multidrug Resistance-Associated Proteins
  • Azithromycin