We assessed the quorum sensing(QS)inhibitory impact of sesamol against the foodborne bacterium Pseudomonas aeruginosa.At concentrations ranging from 50 to 200μg/mL,sesamol significantly inhibited the production of virulence factors such as protease,elastase,pyocyanin,rhamnolipid,and chemotaxis,and improved the susceptibility of bacterial and biofilm cells to colistin.Integrated transcriptomics,metabolomics,and docking analyses indicated that exposure to sesamol destroyed the QS system and down-regulated the expressions of genes encoding virulence and antioxidant enzymes.The down-regulation of genes encoding antioxidant enzymes intensified oxidative stress,as demonstrated by the enhancement of reactive oxygen species and H_(2)O_(2).The enhanced oxidative stress changed the components of the cell membrane,improved its permeability,and ultimately enhanced the susceptibility of bacterial and biofilm cells to colistin.Moreover,exposure to sesamol also led to the disorder of amino acid metabolism and energy metabolism,eventually attenuating the pathogenicity of P.aeruginosa.These findings indicated that sesamol can function as a potent anti-virulence agent to defend against food spoilage caused by P.aeruginosa.
Background:Over the past 50 years,the incidence of obesity has gradually increased,necessitating investigation into the multifactorial contributors to this disease,including the gut microbiota.Bacteria within the human gut microbiome communicate using a density-dependent process known as quorum sensing(QS),in which autoinducer(AI)molecules(e.g.,N-acyl-homoserine lactones[AHLs])are produced to enable bacterial interactions and regulate gene expression.Methods:We aimed to disrupt QS using quorum quenching(QQ)lactonases GcL and SsoPox,which cleave AHL signaling molecules in a taxa-specific manner based on differing enzyme affinities for different substrates.We hypothesized that QQ hinders signals from obesity-associated pathobionts,thereby slowing or preventing obesity.Results:In a murine model of dietinduced obesity,we observed GcL and SsoPox treatments have separate sex-dependent and dose-dependent effects on intestinal community composition and diversity.Notably,male mice given 2 mg/mL SsoPox exhibited significant changes in the relative abundances of gram-negative taxa,including Porphyromonadaceae,Akkermansiaceae,Muribaculaceae,and Bacteroidales(Kruskal-Wallis p<0.001).Additionally,we used covariance matrix network analysis to model bacterial taxa co-occurrence due to QQ enzyme administration.There were more associations among taxa in control mice,particularly among gram-negative bacteria,whereas mice receiving SsoPox had the fewest associations.Conclusions:Overall,our study establishes proof of concept that QQ is a targetable strategy for microbial control in vivo.Further characterization and dosage optimization of QQ enzymes are necessary to harness their therapeutic capability for the treatment of chronic microbial-associated diseases.
辅助基因调控(agr)群体感应系统通过调控毒力因子及生物被膜形成等影响金黄色葡萄球菌毒力的表达。agr的信号传导主要依赖于自诱导信号肽(AIP)与AgrC结合后激活AgrA,而后直接由AgrA或转录后调节因子RNAIII作用于下游靶基因调控金黄色葡萄球菌的毒力因子。本综述主要讲述了AIP与AgrC结合以及AgrA作用于下游靶基因的机制。讨论了agr阴性突变菌株感染对临床患者的影响,还讨论了多种毒力调控基因与agr共同作用调节金葡菌毒力的复杂网络。Accessory gene regulator (agr) quorum sensing network affects the expression of Staphylococcus aureus virulence by regulating virulence factors and biofilm formation. The signal transduction of agr mainly depends on the activation of AgrA after the binding of AIP with AgrC, and then the direct action of AgrA or the post-transcriptional regulatory factor RNAIII on the downstream target gene to regulate the virulence factors of Staphylococcus aureus. This review mainly describes the mechanism of AIP binding to AgrC and AgrA acting on downstream target genes. The effects of agr negative mutant strains on clinical patients were discussed, and the complex network of virulence regulation genes and agr regulating Staphylococcus aureus was discussed.
