Cooperative antibiotic resistance facilitates horizontal gene transfer

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The rise of β-lactam resistance among pathogenic bacteria, due to the horizontal transfer of plasmid-encoded β-lactamases, is a current global health crisis. Importantly, β-lactam hydrolyzation by β-lactamases, not only protects the producing cells but also sensitive neighboring cells cooperatively. Yet, how such cooperative traits affect plasmid transmission and maintenance is currently poorly understood. Here we experimentally show that KPC-2 β-lactamase expression and extracellular activity were higher when encoded on plasmids compared with the chromosome, resulting in the elevated rescue of sensitive non-producers. This facilitated efficient plasmid transfer to the rescued non-producers and expanded the potential plasmid recipient pool and the probability of plasmid transfer to new genotypes. Social conversion of non-producers by conjugation was efficient yet not absolute. Non-cooperative plasmids, not encoding KPC-2, were moderately more competitive than cooperative plasmids when β-lactam antibiotics were absent. However, in the presence of a β-lactam antibiotic, strains with non-cooperative plasmids were efficiently outcompeted. Moreover, plasmid-free non-producers were more competitive than non-producers imposed with the metabolic burden of a plasmid. Our results suggest that cooperative antibiotic resistance especially promotes the fitness of replicons that transfer horizontally such as conjugative plasmids.
OriginalsprogEngelsk
TidsskriftISME Journal
Vol/bind17
Antal sider9
ISSN1751-7362
DOI
StatusUdgivet - 2023

Bibliografisk note

Funding Information:
This work is supported by the Lundbeck Foundation (JSM, R250-2017-1392) and the Marie Sklodowska-Curie grant agreement (No. 794315).

Funding Information:
We would like to thank Prof. Søren J. Sørensen for discussions and feedback. Thanks to Dr. Jakob Russel for advice on statistical analyses. Thanks to Qiqi Fu for helping guide the use of FlowJo. We thank the Lundbeck Foundation for supporting this study (JSM, R250-2017-1392) and the China Scholarship Council for funding QW. AFS would like to thank European Union’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement (No. 794315) for the support.

Publisher Copyright:
© 2023, The Author(s).

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