Abstract: SA-PO0936
MUC1 Transmembrane Glycoprotein Is a Critical Element in the Urinary Tract Host Defense Against Infections
Session Information
- Pathology: Updates and Insights
November 08, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Pathology and Lab Medicine
- 1800 Pathology and Lab Medicine
Authors
- Al-bataineh, Mohammad M., University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States
- Shen, Tian, Columbia University Vagelos College of Physicians and Surgeons, New York, New York, United States
- Xu, Katherine, Columbia University Vagelos College of Physicians and Surgeons, New York, New York, United States
- Kashlan, Ossama B., University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States
- Kidd, Kendrah O., Wake Forest University, Winston-Salem, North Carolina, United States
- Bleyer, Anthony J., Wake Forest University, Winston-Salem, North Carolina, United States
- Barasch, Jonathan M., Columbia University Vagelos College of Physicians and Surgeons, New York, New York, United States
Background
Urinary tract infections (UTIs), predominantly caused by uropathogenic Escherichia coli (UPEC), are among the most prevalent bacterial infections. Increasing antimicrobial resistance and high recurrence rates underscore the need for alternative treatments. Host defense mechanisms in the urinary tract may provide antimicrobial-sparing targets. MUC1, a transmembrane glycoprotein expressed on bladder and kidney epithelia, is involved in host-pathogen interactions, but its role in UTI pathogenesis remains undefined. We hypothesized that MUC1 plays a central role during UTIs by acting as a decoy receptor for bacteria and modulating host immune responses.
Methods
Urinary MUC1 and NGAL were quantified in 75 UTI-positive patients, 75 matched controls, and 52 patients with MUC1 Kidney Disease (MKD; ~50% normal MUC1 expression). Additional studies used Muc1 KO mice and primary renal epithelial cells.
Results
Multiple linear regression analysis revealed that urinary MUC1 levels were significantly influenced by age, UTI status, and NGAL levels. MUC1 was inversely associated with UTI status (p = 0.0008) and positively correlated with NGAL (p = 0.0001), consistent with a protective role. In MKD, female heterozygotes had a significantly higher UTI incidence than genetically unaffected family members (OR = 8.63; p = 0.02). In murine UTI models, Muc1 KO females exhibited increased urothelial damage, inflammation, and bacterial burden compared to WT littermates. PI3K activity, a key regulator of antimicrobial peptides (AMPs) like NGAL, was significantly higher in intercalated cells from WT vs. Muc1 KO kidneys, consistent with elevated NGAL after UPEC infection. In vitro, cleaved MUC1 bound UPEC in a dose-dependent manner and inhibited bacterial adhesion and invasion of primary renal epithelial cells. UPEC growth was suppressed in WT mouse urine, and recombinant MUC1 peptide inhibited UPEC proliferation in M9 minimal medium, demonstrating direct antibacterial activity.
Conclusion
MUC1 acts as both a decoy receptor and physical barrier against UPEC, while enhancing host defense through direct antibacterial activity and PI3K-mediated AMPs production. These findings establish MUC1 as a critical determinant of UTI susceptibility and a potential target for antimicrobial-sparing therapies and diagnostics.
Funding
- NIDDK Support