{
  "id": 14284524,
  "title": "Disruption of cAMP Signalling and RNA Regulation Confers Cefiderocol Resistance in Acinetobacter baumannii",
  "url": "https://urgent.news/2026/10/13/disruption-of-camp-signalling-and-rna-regulation-confers-cefiderocol",
  "topic": "science",
  "section": "Science",
  "published": "2026-10-13T00:00:00.000Z",
  "source": {
    "name": "bioRxiv",
    "slug": "biorxiv",
    "url": "https://www.biorxiv.org/content/10.64898/2026.10.08.755845v1?rss=1"
  },
  "original_language": "en",
  "account": "Cefiderocol, a powerful antibiotic used to fight severe infections caused by drug-resistant bacteria, faces growing challenges due to resistance. In Acinetobacter baumannii, a notorious pathogen, two key factors contribute to this resistance: genetic mutations and changes in RNA regulation. By understanding these mechanisms, researchers can better combat this deadly foe.\n\nMutation of the cAMP-producing enzyme CavA and truncation of the glycine-rich RNA-binding domain in Hfq play significant roles in cefiderocol resistance. These alterations have been found in recent clinical isolates of CRAB, an organism notorious for its drug resistance. Importantly, these genetic changes did not harm the survival of the bacteria in murine models, showcasing their ability to adapt and thrive despite the antibiotic threat.\n\nFurther investigation into these resistance mechanisms revealed that Escherichia coli, another common bacterium, exhibits a similar response. Deletion of the CavA orthologue cyaA in E. coli enhanced its ability to compete against cefiderocol exposure. Additionally, Hfq-dependent regulation of Fur-associated iron homeostasis in A. baumannii was uncovered through integrated omics analysis. This discovery highlights the importance of iron availability in determining the antibiotic susceptibility of the bacteria.\n\nUnder conditions of iron limitation, the truncated form of Hfq induces a defense-primed state in A. baumannii. This state effectively hinders the uptake of siderophores, molecules essential for iron acquisition, and ultimately reduces the effectiveness of cefiderocol. These insights pave the way for improved resistance surveillance and susceptibility testing strategies, crucial for combating the ever-evolving threat of antibiotic-resistant bacteria.",
  "summary": "Cefiderocol is a siderophore-conjugated cephalosporin used to treat severe multidrug-resistant Gram-negative infections. Its recent prioritisation for US national preparedness underscores its clinical importance, yet resistance can emerge despite apparent in vitro susceptibility. Here, we identify two regulatory routes to cefiderocol resistance in carbapenem-resistant Acinetobacter baumannii…",
  "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."
}