Quorum Quenching and the Intestinal Microbiota

Quorum sensing involves chemical signaling among bacteria related to the formation of biofilms and expression of virulence factors. The most common signaling molecules are acyl-homoserine lactones (AHLs), which cause these events to occur once they reach a critical threshold. Quorum quenching is a strategy employed by some bateria in which they produce enzymes that cleave these AHLs and can prevent biofillm formation and attenuate virulence. We are working with Dr. Mikael Elias in the BioTechnology Institute to study the effects of these enzyes in mouse models of disease to determine both their potential clinical efficacy as a treatment and also how specific enzymes can target specific species in a non-bactericidal manner. Preliminary data have indicated sex-specific differences in the activity of these enzymes in protecting against diet-induced obesity. Males were somewhat protected from weight gain when receiving our enzymes SsoPox (more narrow spectrum) or GcL (more broad spectrum), while females saw increased weight gain relative to a control (Figure). Both enzymes reduced compositional differences between sexes.

Schematic of quorum sensing/quenching dynamics.
Representation of AHL-mediated quorum sensing (A and B) and enzymatic quorum quenching (C).
Figure from Rakesh Sikdar & Mikael Elias (2020): Quorum quenching enzymes and their effects on virulence, biofilm, and microbiomes: a review of recent advances, Expert Review of Antiinfective Therapy, doi:10.1080/14787210.2020.1794815

Current Experiments

  • Quorum Quenching as a Therapeutic Lead for Colorectal Cancer
    Recent studies from our group have suggested a potential therapeutic effect of the quorum quenching (QQ) enzyme SsoPox to impact tumor growth and reduce metastatic burden. Research is ongoing to discover mechanisms through which this occurs and optimize QQ as a novel microbiota-based therapeutic strategy.
  • Quorum Quenching Ameliorates Dextran-Sulfate Sodium (DSS)-Induced Colitis
    Patients with inflammatory bowel diseases (IBD) have an altered composition of AHL signaling molecules in the gut, suggesting a role for quorum dynamics in inflammatory conditions. We are testing the efficacy of SsoPox to mitigate DSS-induced colitis in a mouse model.