Targeting uropathogenic Escherichia coli virulence: peanut skin extract as a potential non-antibiotic strategy for Urinary tract infection prevention

Abstract Urinary tract infections (UTI), predominantly caused by uropathogenic Escherichia coli (UPEC), represent a significant global health burden, exacerbated by the rising challenge of antibiotic resistance. Peanut skin extract (PSE), a procyanidin-rich extract with abundant A-type linkages, exhibits anti-UPEC activity. However, its high MIC (10 mg/mL) suggests a predominant anti-virulence mechanism rather than direct bactericidal action. To test this, we evaluated the impact of PSE at sub-inhibitory concentrations (≤1000 μg/mL) on critical UPEC virulence factors. PSE significantly inhibited UPEC motility by downregulating flagella-associated genes (fliC, flhC, and flhD). Adhesion and invasion assays using T24 bladder epithelial cells and Caco-2 intestinal epithelial cells demonstrated PSE's ability to reduce UPEC colonization, likely due to suppressed expression of fimbrial assembly genes (fimC, fimH, papC, and papG). Importantly, PSE disrupted biofilm formation, as evidenced by reduced biofilm mass and downregulation of the biofilm-associated flu gene. In addition, further protein level analysis confirmed a significant reduction in the expression of key virulence factors, including FlhD, FimH, and Ag43. Using a mouse UTI model, PSE intervention reduced bacterial colonization in the bladder and alleviated inflammation, aligning with in vitro findings. These results suggest that PSE mitigates UPEC pathogenicity by targeting virulence factors, offering a promising complementary approach for managing UTI and reducing reliance on antibiotics.