Theoretical and Experimental Investigation of Quorum Sensing Inhibition as an Anti-Virulence Strategy Against Pseudomonas aeruginosa in Nigerian Burn Wound Infections

Quorum sensing (QS) governs the coordinated expression of virulence factors in Pseudomonas aeruginosa, making QS inhibition an attractive anti-virulence strategy against infections resistant to conventional antibiotics, yet QS inhibitor (QSI) research grounded in characterised Nigerian clinical strains from burn wound settings remains entirely absent. This dissertation conducts a theoretical and experimental investigation of QS inhibition as an anti-virulence strategy against Pseudomonas aeruginosa from burn wounds at tertiary hospitals in the North East (Bauchi) and North Central (Benue) zones. Sixty P. aeruginosa isolates from burn wound patients were characterised for QS gene expression (lasI, rhlI, mvfR) by RT-qPCR, biofilm formation, pyocyanin and elastase production, and antibiotic resistance. A library of 12 candidate QSIs including natural plant-derived compounds (Azadirachta indica phenolics, Moringa oleifera flavonoids), synthetic halogenated furanones, and silver nanoparticles were screened for QS inhibitory activity using chromobacterium violacein assays. Selected QSIs were evaluated in in vitro biofilm inhibition, virulence gene downregulation, and galleria mellonella infection models. Plant-derived phenolic extracts demonstrated 67 to 78 percent QS inhibition without bactericidal activity, preserving selective pressure minimisation. Combination of sub-inhibitory ciprofloxacin with the best QSI candidate reduced P. aeruginosa biofilm biomass by 84 percent in vitro. The dissertation develops a QSI-antibiotic combination treatment theory (QACT) specific to Nigerian burn wound clinical isolate characteristics. Keywords: quorum sensing inhibition, Pseudomonas aeruginosa, burn wound, anti-virulence, Nigeria