{
  "id": 10480532,
  "title": "Differential requirement for the Ire1 luminal domain in Candida albicans drug susceptibility and pathogenicity",
  "url": "https://urgent.news/2026/09/28/differential-requirement-for-the-ire1-luminal-domain-in-candida",
  "topic": "science",
  "section": "Science",
  "published": "2026-09-28T00:00:00.000Z",
  "source": {
    "name": "bioRxiv",
    "slug": "biorxiv",
    "url": "https://www.biorxiv.org/content/10.64898/2026.09.24.753484v1?rss=1"
  },
  "original_language": "en",
  "account": "Candida albicans, an opportunistic human pathogen, relies on the unfolded protein response (UPR) for various critical functions such as cell wall integrity, antifungal tolerance, filamentous growth, and virulence. The UPR is regulated by the transmembrane sensor Ire1, which can be activated through two distinct mechanisms: misfolded proteins via its luminal domain or lipid bilayer stress via its transmembrane domain. While in budding yeast these two activation modes lead to different transcriptional programs, the separation of these requirements in C. albicans, where the cell membrane and cell wall are targets for major antifungal drugs, has not been established. To address this, researchers created a strain of C. albicans with an Ire1 lacking an intact luminal domain (ire1{Delta}LD), which could no longer detect proteotoxic stress.\n\nThe ire1{Delta}LD strain exhibited growth in the presence of azole antifungals like fluconazole and miconazole, indicating resistance to these common antifungal agents. However, it showed heightened sensitivity to heat shock, cell wall stress, and the echinocandin caspofungin. Additionally, the strain was unable to maintain filamentous growth and displayed reduced virulence when tested in a Caenorhabditis elegans infection model. RNA sequencing of ire1{Delta}LD cells revealed only minor alterations in the steady-state transcriptome.\n\nThese findings highlight a differential requirement for the input domains of C. albicans Ire1, effectively uncoupling growth under azole-induced membrane stress from the cell wall, thermal, and virulence-associated outcomes that depend on proteotoxic sensing. This distinction may provide valuable insights into developing antifungal strategies that target the UPR more effectively.",
  "summary": "The opportunistic human pathogen Candida albicans depends on the unfolded protein response (UPR) for cell wall integrity, antifungal tolerance, filamentous growth, and virulence. The UPR is driven by the conserved transmembrane sensor Ire1, which is activated either by misfolded proteins through its luminal domain or by lipid bilayer stress (LBS) through its transmembrane domain. In budding…",
  "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."
}