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

关联论文：<strong>调控微调与水平基因转移稳定可移动黏菌素耐药性</strong> 作者：Lois Ogunlana、Liam P. Shaw、Divjot Kaur、Pramod Jangir、Timothy Walsh、Stephan Uphoff 及 R.C. MacLean。预印本版本链接：https://doi.org/10.1101/2022.11.04.515217 <br> 摘要：抗生素耐药性会带来适合度成本，这使得我们难以理解耐药性如何能在病原菌群中长期稳定维持。本研究以mcr-1基因为研究对象，该基因可赋予大肠埃希菌（E. coli）对「最后一线」抗生素黏菌素的耐药性，且自身携带显著的适合度成本。研究结果表明，调控进化对mcr-1的基因表达进行了微调，使大肠埃希菌既能抵消mcr-1带来的适合度成本，同时又能提升对黏菌素的耐药水平。接合性质粒可将低适合度成本的mcr-1等位基因转移至极其多样的大肠埃希菌菌株中，进一步在物种层面稳定了mcr-1的存续。尤为关键的是，在黏菌素作为生长促进剂被禁用、黏菌素使用量下降90%之后，调控突变与猪场中mcr-1稳定性的提升存在显著关联。本研究揭示了耐药基因的快速进化与水平传播如何协同作用，以稳定耐药性，并削弱通过限制使用来降低抗生素耐药性（Antimicrobial Resistance, AMR）的干预措施的效果。 <br> 本存档库保存了https://github.com/liampshaw/mcr1-regulatory-variants/ 的稳定版本（存档时间为2023年3月28日，对应提交哈希值为997a7c88636589147d76a7fd4cd9c08e89825dc8）。本存档库同时包含assemblies.zip压缩包，其中收录了所有存档的基因组组装结果（因文件体积过大，该内容未被上传至GitHub）。 <br> 如需了解文件的更多详细信息，请参阅README.md