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

ABSTRACT: 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 o

SUBMITTER: Liu J 

PROVIDER: S-EPMC11628855 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature