Collateral sensitivity associated with antibiotic resistance plasmids

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 pOXA48. 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.

Automated summary

Collateral sensitivity (CS) is a promising alternative to address the issue of antibiotic resistance (ABR). Recent studies have focused on CS strategies against ABR mediated by chromosomal mutations, but plasmid-mediated ABR also plays a significant role. The research provides new insights for developing CS-informed treatment strategies to combat plasmid-mediated ABR.