Effects Of Quorum Sensing Systems On The Pathogenesis Of Pseudomonas Aeruginosa Pneumonia In Rats

Objective: To understand the importance of quorum sensing system in P. aeruginosa biofilm lung infection, pathogenic effects of the wild-type P. aeruginosa PAO1 and QS double mutants, PAO1 lasI rhlI and PAO1 lasR rhlR were studied and compared in vivo.Methods: Measurements of the MIC and MBC of meropenem (MEM), ciprofloxacin (CIP), ceftazidime (CAZ) in PAO1, lasI rhlI and lasR rhlR mutants in alginate beads and planktonic condition. Examination of the biofilm developments of PAO1, lasI rhlI and lasR rhlR mutants in vitro was performed by means of scanning electronic microscopy (SEM) after three days'incubation. Rats were challenged intratracheally with alginate embedded PA strain PAO1 and the mutatants of QS in the concentration of 1×109 colony-forming units per milliliter [CFU/mL]. One and two weeks post intratracheal challenge with P. aeruginosa, parameters were evaluated.Results :(1) Experiments in vitro: The MIC and MBC of MEM,CIP,CAZ in alginate beads of PAO1, PAO1 lasI rhlI and PAO1 lasR rhlR were double of those in planktonic. After three days'incubation, well-developed biofilm was observed in the PAO1 group, whereas poor biofilm formation was seen in the lasI rhlI and lasR rhlR mutant groups.(2) Experiments in vivo: One week after challenge, significantly milder microscopic and macroscopic lung pathology (P<0.001) and less lung bacterial load (P<0.005, P<0.001) with lower IL-4 (P<0.005),IL-10 (P<0.05, P<0.01) production in the lungs were found in the lasR rhlR mutant group compared to...