New Quorum Sensing System Inhibitor as an Antibacterial Synergist against Multidrug-Resistant .

Development of new bacterial biofilm inhibitors as antibacterial synergists is an effective strategy to solve the resistance of . In this paper, a series of 3-hydroxy-pyridin-4(1)-ones were synthesized and evaluated, and the hit compound () was identified with the effects of inhibiting the production of pyocyanin (IC = 8.6 μM) and biofilm formation (IC = 4.5 μM). Mechanistic studies confirmed that inhibits the formation of bacterial biofilm by inhibiting the expression of , blocking quorum sensing system quinolone biosynthesis. Moreover, we systematically investigated the bactericidal effects of combining currently approved antibiotics for CF including tobramycin, ciprofloxacin, and colistin E with , which showed obvious antibacterial synergy to overcome antibiotics resistance in multidrug-resistant biofilms. The result indicates that compound may be used in the future as a potentially novel antibacterial synergist candidate for the treatment of infections.