mcr-1 regulatory variants

Associated paper: <strong>Regulatory fine-tuning and horizontal gene transfer stabilize mobile colistin resistance </strong> Lois Ogunlana, Liam P. Shaw, Divjot Kaur, Pramod Jangir, Timothy Walsh, Stephan Uphoff, and R.C. MacLean. Preprint version: https://doi.org/10.1101/2022.11.04.515217 <br> Abstract: Antibiotic resistance carries fitness costs, making it difficult to understand how resistance can be stably maintained in pathogen populations over the long term. Here we investigate this problem in the context of mcr-1, a costly gene that confers resistance to the ‘last-resort’ antibiotic colistin in E. coli. Here we show that regulatory evolution has fine-tuned the expression of mcr-1, allowing E. coli to offset the cost of mcr-1 while simultaneously increasing colistin resistance. Conjugative plasmids have transferred low cost mcr-1 alleles across an incredible diversity of E. coli strains, further stabilizing mcr-1 at the species level. Crucially, regulatory mutations were associated with an increased stability of mcr-1 in pigs farms following a ban on the use of colistin as a growth promoter that decreased colistin consumption by 90%. Our study shows how the rapid evolution and horizontal transmission of resistance genes can combine to stabilize resistance and compromise the efficacy of interventions aimed at reducing AMR by limiting consumption. <br> This repository archives a stable version of https://github.com/liampshaw/mcr1-regulatory-variants/ (as of 28/03/2023, commit 997a7c88636589147d76a7fd4cd9c08e89825dc8). It also contains assemblies.zip which contains all assemblies archived (these are missing from github due to file size). <br> For more information on files, see README.md