Novel benzothiazole derivatives target the Gac/Rsm two-component system as antibacterial synergists against Pseudomonas aeruginosa infections

The management of antibiotic-resistant, bacterial biofilm infections in skin wounds poses an increasingly challenging clinical scenario. infection is difficult to eradicate because of biofilm formation and antibiotic resistance. In this study, we identified a new benzothiazole derivative compound, (IC = 43.3 nmol/L), demonstrating remarkable biofilm inhibition at nanomolar concentrations . In further activity assays and mechanistic studies, we formulated an unconventional strategy for combating -derived infections by targeting the two-component (Gac/Rsm) system. Furthermore, slowed the development of ciprofloxacin and tobramycin resistance. By using murine skin wound infection models, we observed that 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 infection . The findings of this study suggest the potential of as a promising antibacterial synergist, highlighting the effectiveness of targeting the two-component system in treating challenging bacterial biofilm infections in humans.