Quorum quenching enzymes disrupt bacterial communication in a sex-and dose-dependent manner  

作　　者：Aneesh Syal Maria Martell Rakesh Sikdar Matthew Dietz Zachary Ziegert Cyrus Jahansouz Mikael H.Elias Christopher Staley 

机构地区：[1]Division of Basic and Translational Research,Department of Surgery,University of Minnesota,Minneapolis,Minnesota,USA [2]BioTechnology Institute,University of Minnesota,St.Paul,Minnesota,USA [3]Department of Biochemistry,Molecular Biology,and Biophysics,University of Minnesota,St.Paul,Minnesota,USA [4]Division of Colon and Rectal Surgery,Department of Surgery,University of Minnesota,Minneapolis,Minnesota,USA

出　　处：《Animal Models and Experimental Medicine》2025年第3期473-482,共10页动物模型与实验医学(英文)

基　　金：Biotechnology Institute and the MnDrive initiative(to MHE)。

摘　　要：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.

关 键 词：MICROBIOME microbiota therapeutics obesity quorum sensing 

分 类 号：R57[医药卫生—消化系统]