RT Journal Article
T1 Multicopy plasmids potentiate the evolution of antibiotic resistance in bacteria
A1 San Millán, Álvaro
A1 Escudero García-Calderón, José Antonio
A1 Gifford, Danna
A1 Mazel, Didier
A1 MacLean, Craig
AB Plasmids are thought to play a key role in bacterial evolution by acting as vehicles for horizontal gene transfer, but the role of plasmids as catalysts of gene evolution remains unexplored. We challenged populations of Escherichia coli carrying the blaTEM-1 β-lactamase gene on either the chromosome or a multicopy plasmid (19 copies per cell) with increasing concentrations of ceftazidime. The plasmid accelerated resistance evolution by increasing the rate of appearance of novel TEM-1 mutations, thereby conferring resistance to ceftazidime, and then by amplifying the effect of TEM-1 mutations due to the increased gene dosage. Crucially, this dual effect was necessary and sufficient for the evolution of clinically relevant levels of resistance. Subsequent evolution occurred by mutations in a regulatory RNA that increased the plasmid copy number, resulting in marginal gains in ceftazidime resistance. These results uncover a role for multicopy plasmids as catalysts for the evolution of antibiotic resistance in bacteria.
PB Nature Research
YR 2016
FD 2016
LK https://hdl.handle.net/20.500.14352/100345
UL https://hdl.handle.net/20.500.14352/100345
LA eng
NO San Millan, A., Escudero, J., Gifford, D. et al. Multicopy plasmids potentiate the evolution of antibiotic resistance in bacteria. Nat Ecol Evol 1, 0010 (2017). https://doi.org/10.1038/s41559-016-0010
NO Centre National de la Recherche Scientifique  (France)
NO European Commission
NO Instituto de Salud Carlos III
DS Docta Complutense
RD 6 abr 2025