Collateral Sensitivity Associated with Antibiotic Resistance Plasmids

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. For CS to be widely applicable in clinica...

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Published inbioRxiv
Main Authors Herencias, Cristina, Rodríguez-Beltrán, Jerónimo, León-Sampedro, Ricardo, Alonso-Del Valle, Aida, Palkovičová, Jana, Cantón, Rafael, Álvaro San Millán
Format Paper
LanguageEnglish
Published Cold Spring Harbor Cold Spring Harbor Laboratory Press 24.11.2020
Subjects
Antibiotic resistance
Antibiotics
Bacteria
Drug resistance
Horizontal transfer
Plasmids
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Summary: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. For CS to be widely applicable in clinical practice, it would need to be effective against the different resistance mechanisms available to bacteria. 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 the selective elimination of plasmid-carrying bacteria. Our results provide new insights that establish the basis for developing CS-informed treatment strategies to combat plasmid-mediated ABR. Competing Interest Statement The authors have declared no competing interest.
DOI:10.1101/2020.07.10.198259