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Abstract Quorum Sensing (QS) Regulates Virulence Factors Expression In Pseudomonas Aeruginosa. Inhibition Of QS-Controlled Virulence Factors Without Inhibiting The Growth Of P. Aeruginosa Is A Promising Target To Overcome The Widespread Resistance. In This Study, We Investigated The Antimicrobial Susceptibility Patterns Of 51 Clinical Isolates Of P. Aeruginosa That Have Been Recovered from Egypt Towards Various Antimicrobials. In Addition, We Detected Different Virulence Factors Of These P. Aeruginosa Isolates, Including Biofilm Formation, Protease Activity, Pyocyanin Production, Rhamnolipids Production, And Compared These Activities With The Standard Strain P. Aeruginosa PAO1 Strain. Also, We Investigated The Impact Of Five Natural Plant Extracts And Four Novel Synthetic Peptides On Biofilm Development, And Some Virulence Factors In P. Aeruginosa. The Results Indicated That Sub-MIC Of The Natural Plant Extracts (Anethum Graveolens Seeds Extract; AGSE, Catharanthus Roseus Leaves Extract; CRLE, Ricinus Communis Leaves Extract; RCLE, Ricinus Communis Seeds Extract; RCSE, And Garlic Juice) As Well As The Four Novel Synthetic Peptides (RIVLHK, RIVRHK, LIVRHK, And LIVRRK) Did Not Affect The Growth Of PAO1 Strain And C45 Isolate As Determined By MIC And Growth Curve Analysis. However, These Stress Factors Significantly Inhibited (P < 0.05) Biofilm Formation And Virulence Factors Production Including Pyocyanin, Protease, And Rhamnolipids. The Transcriptional Changes Associated With QS Were Detected And Found That The Gene Expression Levels Of Lasi, Lasr, Rhli, And Rhlr Were Reduced In Response To Some Of These Stress Factors. Molecular Docking Analysis Revealed That RIVLHK, RIVRHK, LIVRHK, And LIVRRK May Bind To Lasi With Known Structures Mainly Interacting With Their Substrate Binding Sites. This Study Elucidated That LIVRRK And LIVRHK As Novel Synthetic Peptides Are Potent Inhibitors Of Some Virulence Factors In P. Aeruginosa Compared With RIVLHK And RIVRHK. Also, AGSE, CRLE, RCLE, And Garlic Juice Are Effective Inhibitors Of QS, Biofilm Formation, Virulence Factors In P. Aeruginosa, And Have A Potential Effect In Treating Biofilm-Related Infections. |