Exploring the Antivirulence Activity of Pulverulentone A, a Phloroglucinol-Derivative from Leaf Extract, against Multi-Drug Resistant .

(1) Background: Bacterial resistance to antibiotics is a global life-threatening issue. Antivirulence therapy is a promising approach to combat bacterial infections as it disarms the bacteria from their virulence factors with reduced selective pressure and a lower chance of resistance. (2) Methods: leaf extract and its major constituent, Pulverulentone A, were tested for their ability to inhibit biofilm, exopolysaccharides, pyocyanin and proteases produced by MDR . In addition, a larvae model was employed to evaluate the in vivo cytotoxicity of Pulverulentone A and its ability to combat infection. Docking study was further performed to investigate Pulverulentone A druggability against main quorum sensing (QS) targets expressed by ; (3) Results: Both extract and the isolated compound could inhibit biofilm formation, extracellular polymeric substances (EPS) and pigment production by the tested isolates. Unexpectedly, no significant inhibition was observed on proteases production. The in silico docking analysis revealed good interactions of Pulverulentone A with all QS targets examined (LasR, MyfR/PqsR, QscR). Pulverulentone A was safe up to 400 µg·mL in caterpillars. Moreover, -treatment of with Pulverulentone A slightly enhanced the survival of the infected larvae. (4) Conclusions: The present study proves Pulverulentone A safety with significant in vitro and in silico antivirulence potential against .