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Nur77 protects the bladder urothelium from intracellular bacterial infection.
- Source :
-
Nature communications [Nat Commun] 2024 Sep 27; Vol. 15 (1), pp. 8308. Date of Electronic Publication: 2024 Sep 27. - Publication Year :
- 2024
-
Abstract
- Intracellular infections by Gram-negative bacteria are a significant global health threat. The nuclear receptor Nur77 (also called TR3, NGFI-B, or NR4A1) was recently shown to sense cytosolic bacterial lipopolysaccharide (LPS). However, the potential role for Nur77 in controlling intracellular bacterial infection has not been examined. Here we show that Nur77 protects against intracellular infection in the bladder by uropathogenic Escherichia coli (UPEC), the leading cause of urinary tract infections (UTI). Nur77 deficiency in mice promotes the formation of UPEC intracellular bacterial communities (IBCs) in the cells lining the bladder lumen, leading to persistent infection in bladder tissue. Conversely, treatment with a small-molecule Nur77 agonist, cytosporone B, inhibits invasion and enhances the expulsion of UPEC from human urothelial cells in vitro, and significantly reduces UPEC IBC formation and bladder infection in mice. Our findings reveal a new role for Nur77 in control of bacterial infection and suggest that pharmacologic agonism of Nur77 function may represent a promising antibiotic-sparing therapeutic approach for UTI.<br /> (© 2024. The Author(s).)
- Subjects :
- Animals
Humans
Mice
Female
Mice, Inbred C57BL
Mice, Knockout
Phenylacetates
Nuclear Receptor Subfamily 4, Group A, Member 1 metabolism
Nuclear Receptor Subfamily 4, Group A, Member 1 genetics
Urothelium microbiology
Urothelium metabolism
Urothelium drug effects
Urothelium pathology
Uropathogenic Escherichia coli drug effects
Uropathogenic Escherichia coli pathogenicity
Urinary Tract Infections microbiology
Urinary Bladder microbiology
Urinary Bladder pathology
Urinary Bladder metabolism
Urinary Bladder drug effects
Escherichia coli Infections microbiology
Escherichia coli Infections drug therapy
Escherichia coli Infections metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 15
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 39333075
- Full Text :
- https://doi.org/10.1038/s41467-024-52454-8