The management of antibiotic-resistant, bacterial biofilm infections in skin wounds poses an increasingly challenging clinical scenario. Pseudomonas aeruginosa infection is difficult to eradicate because of biofilm formation and antibiotic resistance. In this study, we identified a new benzothiazole derivative compound, SN12 (IC₅₀ = 43.3 nmol/L), demonstrating remarkable biofilm inhibition at nanomolar concentrations in vitro. In further activity assays and mechanistic studies, we formulated an unconventional strategy for combating P. aeruginosa-derived infections by targeting the two-component (Gac/Rsm) system. Furthermore, SN12 slowed the development of ciprofloxacin and tobramycin resistance. By using murine skin wound infection models, we observed that SN12 significantly augmented the antibacterial effects of three widely used antibiotics-tobramycin (100-fold), vancomycin (200-fold), and ciprofloxacin (1000-fold)-compared with single-dose antibiotic treatments for P. aeruginosa infection in vivo. The findings of this study suggest the potential of SN12 as a promising antibacterial synergist, highlighting the effectiveness of targeting the two-component system in treating challenging bacterial biofilm infections in humans.

Objective:To optimize the formula of metronidazole and borneol sustained-release films. Methods: The mass ratio of Rhizoma Bletillae polysaccharide and polyvinyl alcohol 124(PVA-124) and the dosage of glycerol and sodium carboxymethyl cellulose ( CMC-Na) as the influencing factors ,the appearance of films and the release rate of metronidazole at 0. 5h and 4h as the comprehen-sive evaluation indices, the formula of the film-forming materials was optimized by orthogonal test. Results:The mass ratio of Rhizoma Bletillae polysaccharide and PVA-124 was the key factor affecting the quality of the films. When the mass ratio of Rhizoma Bletillae pol-ysaccharide and PVA-124 was 20∶80, and the dosage of glycerol was 3. 5g and that of CMC-Na was 0. 14g, the appearance of the films was satisfied, the release rate of metronidazole at 0. 5h and 4h was 25. 17% and 69. 64%, respectively, and the average cumulative re-lease rate at 8h was over 90%. Conclusion:The films prepared by the optimized formula are flat, smooth, clean and moderately soft, which can not only remain the drug release characteristics of the films made by the original formula, but also exhibit the pharmacologi-cal effect of Rhizoma Bletillae.