DOI: 10.1002/ame2.12520
Quorum quenching enzymes disrupt bacterial communication in a sex-and dose-dependent manner
Aneesh Syal1
Maria Martell1
Rakesh Sikdar2
Matthew Dietz1
Zachary Ziegert1
Cyrus Jahansouz3
Mikael H.Elias2
Christopher Staley1
1.Division of Basic and Translational Research,Department of Surgery,University of Minnesota,Minneapolis,Minnesota,USA;BioTechnology Institute,University of Minnesota,St.Paul,Minnesota,USA2.BioTechnology Institute,University of Minnesota,St.Paul,Minnesota,USA;Department of Biochemistry,Molecular Biology,and Biophysics,University of Minnesota,St.Paul,Minnesota,USA3.Division of Colon and Rectal Surgery,Department of Surgery,University of Minnesota,Minneapolis,Minnesota,USA
摘要：Background:Over the past 50years,the incidence of obesity has gradually increased,necessitating investigation into the multifactorial contributors to this disease,includ-ing 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 bac-terial 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 dif-fering 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 diet-induced 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 2mg/mL SsoPox exhibited significant changes in the relative abundances of gram-negative taxa,in-cluding 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 bac-teria,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 optimi-zation of QQ enzymes are necessary to harness their therapeutic capability for the treatment of chronic microbial-associated diseases.
机标关键词：communicationquorumbacterialdisruptdose-dependentenzymesmannerquenching
论文发表日期：2025-03-30
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：10( 473-482 )
英文信息