Antivirulence Activity of a Dietary Phytochemical: Hibiscus Acid Isolated from Hibiscus sabdariffa L. Reduces the Virulence of Pseudomonas aeruginosa in a Mouse Infection Model

L. ( ) calyxes, rich in organic acids, are included in diets in different countries. In recent years, some phytochemicals have been shown to reduce bacterial virulence at sublethal concentrations by interfering with quorum sensing (QS) systems. Therefore, in this study the antivirulence properties of calyxes and two -lactones (hibiscus acid [HA] and its methyl ester) in were analyzed. Acetone and methanol extracts of showed anti-QS activity by inhibiting violacein production (60% to 80% with 250 g/mL). In molecular docking analysis, the -lactones registered a good binding score, which suggests strong interaction with the active site of LasR protein. To verify their effect , they were isolated from and evaluated in six QS-regulated phenotypes, as well as in ExoU toxin that is released by the type III secretion system (T3SS). At 500 g/mL they reduced alkaline protease (29-52%) and elastase (15-37%) activity, biofilm formation (∼75%), and swarming (50%), but there was no effect on pyocyanin production, hemolytic activity, or type III secretion. In a mouse abscess/necrosis model, HA at sublethal concentrations (15 and 31.2 g/mL) affected infection establishment and prevented damage and systemic spread. In conclusion, HA is the first molecule identified with antivirulence properties in with the potential to prevent infections caused by .