Collateral sensitivity associated with antibiotic resistance plasmids
- Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Spain
- Faculty of Veterinary Hygiene and Ecology, University of Veterinary and Pharmaceutical Sciences, Czech Republic
- Centro Nacional de Biotecnología-CSIC, Spain
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.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for Figures 1, 2, 3 and S2.Sequencing data have been deposited in the Sequence Read Archive (SRA) repository, BioProject ID: PRJNA644278 (https://www.ncbi.nlm.nih.gov/bioproject/644278).
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DNA Sequence DataSequence Read Archive (SRA) repository, Bioproject PRJNA644278.
Article and author information
Author details
Jerónimo Rodríguez-Beltrán
Ricardo León-Sampedro
Funding
European Research Council (ERC-StG 757440-PLASREVOLUTION)
- Álvaro San Millán
Instituto de Salud Carlos III (PI16-00860)
- Álvaro San Millán
Agencia Estatal de Investigación (IJC2018-035146-I)
- Jerónimo Rodríguez-Beltrán
Instituto de Salud Carlos III (MS15-00012)
- Álvaro San Millán
Comunidad Autonoma de Madrid (PEJD-2018-POST/BMD-8016)
- Cristina Herencias
European Commission (R-GNOSIS-FP7-HEALTH-F3-2011-282512)
- Rafael Cantón
Instituto de Salud Carlos III (REIPIR D16/0016/0011)
- Rafael Cantón
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Marc Lipsitch, Harvard TH Chan School of Public Health, United States
Version history
- Received: November 24, 2020
- Accepted: January 20, 2021
- Accepted Manuscript published: January 20, 2021 (version 1)
- Version of Record published: January 26, 2021 (version 2)
Copyright
© 2021, Herencias et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Collateral sensitivity associated with antibiotic resistance plasmids
eLife 10:e65130.
https://doi.org/10.7554/eLife.65130
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