Study On Quorum Sensing Meditated Evolution Mechanism Of Pseudomonas Aeruginosa Resistance

Antibiotic resistance is one of the most serious public health problems in the world.Although important progress has been made on the study of microbial antibiotic resistance mechanisms,there are relatively few studies illustrating the evolution mechanism of microbial resistance evolution.Previous studies have shown that biofilms are essential for microbial antibiotic resistance and are regulated by quorum sensing.However,the role of quorum sensing played in the evolution of antibiotic resistance is currently unknown.Based on this,our study,through long-term evolutionary experiments,short-term response experiments,comparisons of transcriptome and mutant construction,preliminarily explored the role and mechanism of quorum sensing in antibiotic resistance evolution.This research not only helps to understand the mechanism of microbial resistance evolution,but also provides a reference for the prevention and control of microbial antibiotic resistance.The main conclusions of this study are as follows:(1)In the resistance evolution under sublethal concentrations of ciprofloxacin and azithromycin,the evolution ability of WT strains was stronger than that of quorum-sensing mutants(35)lasR,(35)rhlR and(35)pqsR.WT and quorum sensing mutants did not have significant differences in antibiotic resistance evolution under the sublethal concentrations of ceftazidime and amikacin.Quorum sensing was involved in the evolution of ciprofloxacin and azithromycin resistance,and there was no siginificant difference on the evolution of resistance under the selection of ceftazidime and amikacin.(2)Ciprofloxacin and azithromycin significantly inhibit the expressions of lasI,lasR,rhlI,rhlR genes,the signaling molecules secretion of 3OC12-HSL and C4-HSL,elatease and rhamnolipid.The inhibition of ciprofloxacin for quorum sensing systems has a dose effect,and there is no dose relationship between azithromycin and the response of quorum sensing.Ceftazidime and amikacin have little effect on the synthesis of quorum sensing genes,signaling molecules and public substances.(3)During the resistance evolution under the stress of ciprofloxacin,the LasIR,RhlIR and PQS quorum sensing systems all increased significantly,and the PQS system increased most significantly.The resistance level of wild strain was 8 times higher than that of pyocyanin mutants.The secretion of pyocyanin plays a key role in the evolution of quorum sensing meditated ciprofloxacin resistance.The quorum sensing and pyocyanin did not play a significant role in the evolution of ceftazid resistance.