Emerging patterns of plasmid-host coevolution that stabilize antibiotic resistance

Thibault Stalder, Linda M. Rogers, Chris Renfrow, Hirokazu Yano, Zachary Smith, Eva M. Top

Research output: Contribution to journalArticlepeer-review

35 Citations (Scopus)


Multidrug resistant bacterial pathogens have become a serious global human health threat, and conjugative plasmids are important drivers of the rapid spread of resistance to last-resort antibiotics. Whereas antibiotics have been shown to select for adaptation of resistance plasmids to their new bacterial hosts, or vice versa, a general evolutionary mechanism has not yet emerged. Here we conducted an experimental evolution study aimed at determining general patterns of plasmid-bacteria evolution. Specifically, we found that a large conjugative resistance plasmid follows the same evolutionary trajectories as its non-conjugative mini-replicon in the same and other species. Furthermore, within a single host-plasmid pair three distinct patterns of adaptive evolution led to increased plasmid persistence: i) mutations in the replication protein gene (trfA1); ii) the acquisition by the resistance plasmid of a transposon from a co-residing plasmid encoding a putative toxin-antitoxin system; iii) a mutation in the host's global transcriptional regulator gene fur. Since each of these evolutionary solutions individually have been shown to increase plasmid persistence in other plasmid-host pairs, our work points towards common mechanisms of plasmid stabilization. These could become the targets of future alternative drug therapies to slow down the spread of antibiotic resistance.

Original languageEnglish
Article number4853
JournalScientific reports
Issue number1
Publication statusPublished - 2017 Dec 1
Externally publishedYes

ASJC Scopus subject areas

  • General


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