Antibiofilm activity of benzophenone-2 against uropathogenic Escherichia coli

AIMS: Uropathogenic Escherichia coli (UPEC) is the leading cause of urinary tract infections, with biofilm formation playing a critical role in infection recurrence. The increasing prevalence of multidrug-resistant UPEC underscores the need for alternative strategies that target biofilms without imposing strong evolutionary pressure typical of conventional antibiotics This study identifies 2,2',4,4'-Tetrahydroxybenzophenone, also known as benzophenone-2 (BP-2), a UV filter widely used in sunscreens and cosmetic products as a promising candidate for repurposing as an antibiofilm agent against UPEC. METHODS: BP-2 was evaluated for its antibiofilm activity against UPEC, as well as its ability to inhibit key virulence factors, including curli production, rugosity, and motility. Additionally, in vivo, in vitro, and in silico toxicity assessments were performed, along with 3D-QSAR analysis and molecular docking. RESULTS: BP-2 exhibited a minimum inhibitory concentration of 600 μg mL-1 and inhibited over 50% and 80% of UPEC biofilm formation at sub-inhibitory concentrations of 20 and 100 μg mL-1, respectively, without affecting bacterial growth or viability. Furthermore, BP-2 disrupted mature UPEC biofilms, impaired motility, rugose colony formation, and curli biogenesis, and showed antimicrobial activity against other pathogens. qRT-PCR demonstrated downregulation of curli biogenesis and motility related virulence genes while molecular docking suggested inhibition of the curli master regulator CsgD. 3D-QSAR analysis emphasized the role of hydroxyl substitutions at the 2nd and 4th positions of the benzophenone scaffold. CONCLUSIONS: BP-2 possesses potent antibiofilm activity against UPEC by targeting key virulence factors without affecting bacterial viability and has potential as a promising antibiofilm candidate for the treatment of UPEC-associated infections.