4.5 Article

Intra- and interpopulation transposition of mobile genetic elements driven by antibiotic selection

Journal

NATURE ECOLOGY & EVOLUTION
Volume 6, Issue 5, Pages 555-+

Publisher

NATURE PORTFOLIO
DOI: 10.1038/s41559-022-01705-2

Keywords

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Funding

  1. National Institutes of Health [R01A1125604, R01GM110494, R01EB029466]
  2. National Science Foundation [MCB-1937259]
  3. David and Lucile Packard Foundation

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Antibiotic selection accelerates the spread of antibiotic resistance genes by increasing the proportion of cells carrying the resistance on plasmids, which have higher expression of the resistance genes and thus higher survival rates when facing antibiotic selection.
The spread of genes encoding antibiotic resistance is often mediated by horizontal gene transfer (HGT). Many of these genes are associated with transposons, a type of mobile genetic element that can translocate between the chromosome and plasmids. It is widely accepted that the translocation of antibiotic resistance genes onto plasmids potentiates their spread by HGT. However, it is unclear how this process is modulated by environmental factors, especially antibiotic treatment. To address this issue, we asked whether antibiotic exposure would select for the transposition of resistance genes from chromosomes onto plasmids and, if so, whether antibiotic concentration could tune the distribution of resistance genes between chromosomes and plasmids. We addressed these questions by analysing the transposition dynamics of synthetic and natural transposons that encode resistance to different antibiotics. We found that stronger antibiotic selection leads to a higher fraction of cells carrying the resistance on plasmids because the increased copy number of resistance genes on multicopy plasmids leads to higher expression of those genes and thus higher cell survival when facing antibiotic selection. Once they have transposed to plasmids, antibiotic resistance genes are primed for rapid spread by HGT. Our results provide quantitative evidence for a mechanism by which antibiotic selection accelerates the spread of antibiotic resistance in microbial communities. Analysing the transposition dynamics of synthetic and natural transposons that encode resistance to different antibiotics, the authors show that stronger antibiotic selection leads to a higher fraction of cells carrying the resistance on plasmids.

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