{
  "id": 9655054,
  "title": "Using population-level whole-genome sequencing to profile colistin resistance evolution dynamics in diverse clinical Pseudomonas aeruginosa lineages",
  "url": "https://urgent.news/2026/09/24/using-population-level-whole-genome-sequencing-to-profile-colistin",
  "topic": "science",
  "section": "Science",
  "published": "2026-09-24T00:00:00.000Z",
  "source": {
    "name": "bioRxiv",
    "slug": "biorxiv",
    "url": "https://www.biorxiv.org/content/10.64898/2026.09.22.753656v1?rss=1"
  },
  "original_language": "en",
  "account": "Colistin, a vital antibiotic for combating multidrug-resistant Pseudomonas aeruginosa infections, particularly in chronic respiratory diseases, has a resistome that has not been fully explored. Most previous studies have centered on the PAO1 strain. In this study, researchers utilized experimental evolution to subject nine P. aeruginosa lineages, each with distinct clinical presentations and genetic backgrounds, to escalating colistin pressure. Samples were collected from broth cultures at varying colistin concentrations, from 0.0625 to 512 g/mL. The team identified several known and novel genetic mutations responsible for colistin resistance, alongside compensatory mutations present at low allele frequencies (5% or less). Despite their diverse origins, all lineages independently evolved mutations in the pmrAB two-component system, often in conjunction with phoPQ variants. Once the typical transposase cassette (TCS) remodeling plateaued, populations began to display secondary driver mutations, primarily in the lipid A-modifying gene, lpxO2. Alongside these AMR driver mutations, strains also evolved complex adaptive strategies to counteract severe colistin-induced oxidative and metabolic stress. These adaptations included the emergence of hypermutators and changes to DNA and protein repair networks. The study also revealed convergent regulatory alterations in the cyclic-di-GMP network and central metabolism pathways, serving as compensatory mechanisms to facilitate biofilm formation and offset the fitness costs associated with colistin resistance. By employing a mixture-aware population genomics approach, the researchers captured intense clonal interference and transient tolerance mutations that would be overlooked by conventional end-point analysis methods.",
  "summary": "Colistin (CST) is a critical last-line antibiotic for treating multidrug-resistant Pseudomonas aeruginosa infections, especially in chronic respiratory disease. Despite its clinical importance, the P. aeruginosa CST resistome remains incompletely characterised, with most studies focusing on the PAO1 prototypic strain. Here, we used experimental evolution to apply stepwise CST selective pressure…",
  "key_points": [],
  "editors_take": null,
  "illustration": null,
  "coverage": {
    "outlets": 1,
    "also_reported_by": []
  },
  "ai_generated": true,
  "disclaimer": "Summaries, key points and the editor’s take are written by software from other outlets’ reporting and may contain errors — always check the linked original."
}