{
  "id": 12281100,
  "title": "Mycobacterium tuberculosis inactivates host oxysterols to impair macrophage cholesterol homeostasis",
  "url": "https://urgent.news/2026/10/05/mycobacterium-tuberculosis-inactivates-host-oxysterols-to-impair",
  "topic": "science",
  "section": "Science",
  "published": "2026-10-05T00:00:00.000Z",
  "source": {
    "name": "bioRxiv",
    "slug": "biorxiv",
    "url": "https://www.biorxiv.org/content/10.64898/2026.10.04.756586v1?rss=1"
  },
  "original_language": "en",
  "account": "Mycobacterium tuberculosis (Mtb) hijacks host oxysterol signaling to manipulate macrophage cholesterol management, as demonstrated in a recent study. The pathogen generates enzymatic oxysterol inactivation, targeting the endogenous oxysterols 27-hydroxycholesterol (27-HC) and 3{beta}-hydroxycholest-5-enoic acid (3{beta}-HCA). This leads to the formation of new metabolites, 27-hydroxycholest-4-en-3-one (27-HCO) and 3-oxocholest-4-enoic acid (3O-CA), which accumulate in sputum lipidomics from TB patients across three continents during active disease. Treatment reverts these metabolic signatures to normal levels. In human macrophages, Mtb 3{beta}-hydroxysteroid dehydrogenase (3{beta}-Hsd) converts 3{beta}-HCA to 27-HCO. Unlike the parent oxysterols, these new compounds do not activate liver X receptor (LXR) or suppress sterol regulatory element-binding protein 2 (SREBP2) target genes. Consequently, Mtb's enzymatic oxysterol inactivation hinders macrophage cholesterol homeostasis, resulting in a phenotype where the bacteria can thrive. The restoration of this disrupted homeostasis occurs with LXR antagonism, highlighting the crucial role of Mtb's oxysterol inactivation in its pathogenicity.",
  "summary": "Host oxysterols coordinate macrophage cholesterol homeostasis and antimicrobial defense, but whether pathogens directly target oxysterol signaling is unknown. Here, we identify pathogen-mediated enzymatic oxysterol inactivation as a mechanism by which Mycobacterium tuberculosis (Mtb) subverts host cholesterol metabolism. Mtb oxidizes the endogenous oxysterols 27-hydroxycholesterol (27-HC) and…",
  "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."
}