Plasmid- and strain-specific factors drive variation in ESBL-plasmid spread in vitro and in vivo

Benz, Fabienne and Huisman, Jana S. and Bakkeren, Erik and Herter, Joana A. and Stadler, Tanja and Ackermann, Martin and Diard, Médéric and Egli, Adrian and Hall, Alex R. and Hardt, Wolf-Dietrich and Bonhoeffer, Sebastian. (2021) Plasmid- and strain-specific factors drive variation in ESBL-plasmid spread in vitro and in vivo. The ISME journal, 15 (3). pp. 862-878.

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Horizontal gene transfer, mediated by conjugative plasmids, is a major driver of the global rise of antibiotic resistance. However, the relative contributions of factors that underlie the spread of plasmids and their roles in conjugation in vivo are unclear. To address this, we investigated the spread of clinical Extended Spectrum Beta-Lactamase (ESBL)-producing plasmids in the absence of antibiotics in vitro and in the mouse intestine. We hypothesised that plasmid properties would be the primary determinants of plasmid spread and that bacterial strain identity would also contribute. We found clinical Escherichia coli strains natively associated with ESBL-plasmids conjugated to three distinct E. coli strains and one Salmonella enterica serovar Typhimurium strain. Final transconjugant frequencies varied across plasmid, donor, and recipient combinations, with qualitative consistency when comparing transfer in vitro and in vivo in mice. In both environments, transconjugant frequencies for these natural strains and plasmids covaried with the presence/absence of transfer genes on ESBL-plasmids and were affected by plasmid incompatibility. By moving ESBL-plasmids out of their native hosts, we showed that donor and recipient strains also modulated transconjugant frequencies. This suggests that plasmid spread in the complex gut environment of animals and humans can be predicted based on in vitro testing and genetic data.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Infection Biology > Pathogen Evolution (Diard)
UniBasel Contributors:Diard, Médéric and Egli, Adrian
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Springer nature
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:01 Dec 2021 11:25
Deposited On:30 Dec 2020 13:50

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