| Autor: |
Ismail MM; Microbiology and Immunology Department, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt., Hassan M; Microbiology and Immunology Department, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt., Moawad SS; Department of Pests and Plant Protection, National Research Center (NRC), Giza 12622, Egypt., Okba MM; Pharmacognosy Department, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt., Ashour RM; Pharmacognosy Department, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt., Fayek NM; Pharmacognosy Department, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt., Saber FR; Pharmacognosy Department, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt. |
| Abstrakt: |
(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: Callistemon citrinus leaf extract and its major constituent, Pulverulentone A, were tested for their ability to inhibit biofilm, exopolysaccharides, pyocyanin and proteases produced by MDR P. aeruginosa . In addition, a Galleria mellonella larvae model was employed to evaluate the in vivo cytotoxicity of Pulverulentone A and its ability to combat Pseudomonas infection. Docking study was further performed to investigate Pulverulentone A druggability against main quorum sensing (QS) targets expressed by P. aeruginosa ; (3) Results: Both C. citrinus 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 -1 in Galleria caterpillars. Moreover, pre -treatment of P. aeruginosa 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 P. aeruginosa . |
