Developing Novel Sulfonyl AHL Synthase Inhibitors to Inhibit Quorum Sensing in B.Japonicum
Faculty Mentor Information
Dr. Eric Brown, Boise State University
Presentation Date
7-16-2026
Abstract
Novel development of antibiotics continues to decline, as bacteria mutate faster than cures can be developed, resulting in a resistance to antibiotic therapy. A new form of therapy focuses on inhibiting quorum sensing. Quorum sensing is a form of bacterial cell-to-cell communication using autoinducers, which allow them to determine the quantity of neighboring bacteria of their species. Once the autoinducers reach a specific density threshold, the genetic expression of the bacteria changes, causing virulence. AHL (N-acyl homoserine lactones) are a subset of autoinducers produced by AHL synthase, critical to QS in gram negative bacteria. We aim to synthesize 32 novel sulfonyl based inhibitors, with a similar structure to AHL’s in b.japonicum, verified using H-1 and C-13 NMR techniques, that inhibit the AHL synthase enzyme. We collaborated with Dr. Nagarajan’s research project where they will test our synthesized compounds for their effectiveness at inhibition.
The development of novel antibiotics has continued to decline while bacterial resistance to existing therapies has increased, highlighting the need for alternative antimicrobial strategies. One approach is to inhibit quorum sensing, a bacterial communication system that uses autoinducers to regulate gene expression in response to population density. In many Gram-negative bacteria, N-acyl homoserine lactones, or AHLs, function as key autoinducers and are synthesized by AHL synthase enzymes. This project focuses on the synthesis of novel enantiomerically pure D-sulfonyl-based compounds designed to structurally resemble AHLs in Bradyrhizobium japonicum and inhibit AHL synthase activity. The synthesized compounds will be characterized using ^¹H and ^¹³C NMR spectroscopy to confirm their structures. These compounds will be tested for their ability to inhibit AHL synthase and disrupt quorum sensing in B. japonicum. These studies may support the development of quorum-sensing inhibitors as alternatives or complements to traditional antibiotic therapies.
Developing Novel Sulfonyl AHL Synthase Inhibitors to Inhibit Quorum Sensing in B.Japonicum
Novel development of antibiotics continues to decline, as bacteria mutate faster than cures can be developed, resulting in a resistance to antibiotic therapy. A new form of therapy focuses on inhibiting quorum sensing. Quorum sensing is a form of bacterial cell-to-cell communication using autoinducers, which allow them to determine the quantity of neighboring bacteria of their species. Once the autoinducers reach a specific density threshold, the genetic expression of the bacteria changes, causing virulence. AHL (N-acyl homoserine lactones) are a subset of autoinducers produced by AHL synthase, critical to QS in gram negative bacteria. We aim to synthesize 32 novel sulfonyl based inhibitors, with a similar structure to AHL’s in b.japonicum, verified using H-1 and C-13 NMR techniques, that inhibit the AHL synthase enzyme. We collaborated with Dr. Nagarajan’s research project where they will test our synthesized compounds for their effectiveness at inhibition.
The development of novel antibiotics has continued to decline while bacterial resistance to existing therapies has increased, highlighting the need for alternative antimicrobial strategies. One approach is to inhibit quorum sensing, a bacterial communication system that uses autoinducers to regulate gene expression in response to population density. In many Gram-negative bacteria, N-acyl homoserine lactones, or AHLs, function as key autoinducers and are synthesized by AHL synthase enzymes. This project focuses on the synthesis of novel enantiomerically pure D-sulfonyl-based compounds designed to structurally resemble AHLs in Bradyrhizobium japonicum and inhibit AHL synthase activity. The synthesized compounds will be characterized using ^¹H and ^¹³C NMR spectroscopy to confirm their structures. These compounds will be tested for their ability to inhibit AHL synthase and disrupt quorum sensing in B. japonicum. These studies may support the development of quorum-sensing inhibitors as alternatives or complements to traditional antibiotic therapies.