Abstract
Plasmids may maintain antibiotic resistance genes in bacterial populations through conjugation, in the absence of direct selection pressure. However, the costs and benefits of conjugation for plasmid and bacterial fitness are not well understood. Using invasion and competition experiments with plasmid mutants we explicitly tested how conjugation contributes to the maintenance of a plasmid bearing a single extended-spectrum ß-lactamase (ESBL) gene (blaCTX-M-14). Surprisingly, conjugation had little impact on overall frequencies, although it imposed a substantial fitness cost. Instead, stability resulted from the plasmid conferring fitness benefits when rare. Frequency dependent fitness did not require a functional blaCTX-M-14 gene, and was independent of culture media. Fitness benefits when rare are associated with the core plasmid backbone but are able to drive up frequencies of antibiotic resistance because fitness burden of the blaCTX-M-14 gene is very low. Negative frequency dependent fitness can contribute to maintaining a stable frequency of resistance genes in the absence of selection pressure from antimicrobials. In addition, persistent, low cost resistance has broad implications for antimicrobial stewardship.
Highlights
Plasmids may maintain antibiotic resistance genes in bacterial populations through conjugation, in the absence of direct selection pressure
Understanding the selection pressures that maintain antimicrobial resistance (AMR) genes is key to understanding how resistance will respond to antibiotic usage and how we might develop interventions to extend the use of antibiotics in the face of resistance
Even when selection pressure is intense AMR genes may not rise to fixation[4]
Summary
Plasmids may maintain antibiotic resistance genes in bacterial populations through conjugation, in the absence of direct selection pressure. If rates of horizontal transfer (conjugation) are sufficient to offset fitness cost of carriage or loss from segregation, plasmids may be stable or capable of increasing in frequency in bacterial populations without selection from antibiotic usage[2,8]. In the wild type pCT transconjugants made up a substantial proportion of plasmid carriers after only five transfers (Fig. 1C), indicating that the similarities between conjugative and non-conjugative plasmids were not the result of low conjugation.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have