Synthesis and Assay of Vibrio Quorum Sensing Inhibitors

Area of Science:

• Microbiology
• Medicinal Chemistry
• Biochemistry

Background:

• Bacteria utilize quorum sensing for cell-cell communication to regulate group behaviors.
• LuxR/HapR transcription factors in Vibrio species control numerous genes impacting virulence and metabolism.
• Thiophenesulfonamides are effective inhibitors of LuxR/HapR, blocking quorum sensing gene expression.

Purpose of the Study:

• To develop an educational platform for college students to integrate chemistry and biology skills.
• To create a course-based undergraduate research experience (CURE) focused on quorum sensing inhibition.
• To design, synthesize, and test novel thiophenesulfonamide inhibitors of Vibrio LuxR/HapR.

Main Methods:

• Students designed and synthesized small molecule inhibitors based on the thiophenesulfonamide scaffold.
• Computational structural modeling was used to predict the binding affinity of synthesized compounds.
• Microbiological assays in E. coli and Vibrio species were performed to evaluate compound efficacy.

Main Results:

• Optimized protocols were established for a year-long, multi-disciplinary CURE.
• A reporter assay in E. coli was developed to predict compound efficacy against target proteins.
• The study demonstrates a successful integration of chemical synthesis, computational modeling, and biological assays.

Conclusions:

• The developed CURE effectively engages students in authentic scientific research.
• Thiophenesulfonamide-based compounds show promise as inhibitors of bacterial quorum sensing.
• This educational model facilitates the assimilation of diverse scientific skills in undergraduates.