Study On Preparation Of Antibacterial Silver Nanoparticles And Quorum Sensing Effect Of AI-2 Inhibitors On PAO1

The abuse of antibiotics has accelerated the emergence of antibiotic-resistant bacteria,posing a global threat to human health: the treatment of diseases caused by "super bacteria" is facing great challenges.Nowadays,it is urgent for discovering the novelty antibacterial agents.Nanomaterials have promising potential as antimicrobial materials,and enrich in infection areas through certain targeting mechanisms,showing high effects against bacteria.Moreover,acting on bacterial cell wall directly is responsible for little cross-resistance as nanomaterials avoid affecting the cytoplasm.The Quorum Sensing（QS）has been regarded as a novel strategy to decrease bacterial infection and resistance.The inhibitor of QS（Quorum Sensing Inhibitor,QSI）can prevent communication intra-or inter-bacteria,down-regulate the expression of bacteria virulence factors and decrease bacteria pathogenicity.In addition,QSI possesses little selective pressure on bacteria,which reduces bacteria drug resistance to some extent.This research focus on the effect of Silver Nanoparticles（Ag NPs）on some pathogenic bacteria,and the effect of AI-2（Autoinducer-2）quorum sensing inhibitor str7410 acting on the QS of P.aeruginosa PAO1.In the part one,the chemical compound Ag NPs were synthesized and the antibacteria activities were determined.Glucose or sweet orange oil was used as reductant in the reaction,respectively.Several variables,including types of stabilizer,time of the reaction,the dosage of reductant etc.were investigated to optimize a safe,efficient,and controlled method for Ag NPs preparation.Moreover,antibacterial activities of Ag NPs were screened through the disk-diffusion method,and the Minimal Inhibitory Concentration（MIC）.Ag NPs prepared by sweet orange oil as reductant possessed higher antimicrobial activities compared with that of glucose as reductant,and Ag NPs with much more smaller particle sizes showed much more higher antimicrobial activities.In addition,both kinds of Ag NPs had a higher inhibition effect against Gram-negative bacteria,comparing with that of Gram-positive bacteria.In the part two,str7410,a QSI against AI-2,were extensively investigated its effect on QS of P.aeruginosa PAO1 in vitro and in vivo.In vitro,bacteria growth studies showed no toxicity inhibitory effect at common the working concentrations.Studies on central QS-regulated indicators provided compound Str7410 could reduce expressions of virulence factors,lead the down-regulation of the swarming movement of PAO1,and also successfully lead to the eradication of PAO1 biofilms.In vivo,str7410 combined with could significantly increase the survival rate of C.elegans N2 infected by PAO1.In summary,this study evaluated a bioactivity analysis of Ag NPs and AI-2quorum sensing inhibitor str7410 via in vitro and in vivo experiments.It suggested that Ag NPs prepared by sweet orange oil reductant possessed excellent antibacterial effect on Gram-negative bacteria,and str7410 performed a significant inhibitory effect on QS of PAO1,respectively.In a word,it developed a simple,economic,efficient,and low-toxic method for Ag NPs preparation,and pointed to the potential of the small molecule str7410 as promising entities for antimicrobial drug development.