Collateral sensitivity associated with antibiotic resistance plasmids

Elife. 2021 Jan 20;10:e65130. doi: 10.7554/eLife.65130.

Abstract

Collateral sensitivity (CS) is a promising alternative approach to counteract the rising problem of antibiotic resistance (ABR). CS occurs when the acquisition of resistance to one antibiotic produces increased susceptibility to a second antibiotic. Recent studies have focused on CS strategies designed against ABR mediated by chromosomal mutations. However, one of the main drivers of ABR in clinically relevant bacteria is the horizontal transfer of ABR genes mediated by plasmids. Here, we report the first analysis of CS associated with the acquisition of complete ABR plasmids, including the clinically important carbapenem-resistance conjugative plasmid pOXA-48. In addition, we describe the conservation of CS in clinical E. coli isolates and its application to selectively kill plasmid-carrying bacteria. Our results provide new insights that establish the basis for developing CS-informed treatment strategies to combat plasmid-mediated ABR.

Keywords: E. coli; antibiotics; collateral sensitivity; evolutionary biology; infectious disease; microbiology; plasmid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Carbapenems / pharmacology*
  • Drug Collateral Sensitivity*
  • Drug Resistance, Multiple, Bacterial / genetics*
  • Escherichia coli / drug effects*
  • Escherichia coli / genetics
  • Plasmids / drug effects
  • Plasmids / physiology*

Substances

  • Anti-Bacterial Agents
  • Carbapenems

Grant support

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.