Synthesis and Evaluation of Indole Based Molecules on V. Cholerae QS Pathways

Bacteria have the ability to communicate with one another by secreting and detecting small molecules called autoinducers (AI). This communication pathway, termed quorum sensing (QS), enables bacteria to react synchronously to changes in cell density in order to coordinate population-wide virulence factor production, biofilm formation, and antibiotic resistance.

While most AIs serve intra-species communication, some are responsible for interspecies and even interkingdom communication; indoles have been proposed to serve such a role, as it is produced by more than 85 species of bacteria, plants and insects, and can be found in sweat, urine, guts, lungs and even brains of mammals. This study focuses on the relationship between V. cholerae and indole secretion and recognition; V. cholerae affects the human body, especially in the gut, where indole concentrations can reach 250–1100 μM. Since indole can bind the endogenous receptor (CqsS) for the primary V. cholerae autoinducer (CAI-1) - we designed, synthesized and evaluated a library of indole-CAI-1 derivatives in order to modulate QS pathways and virulence in this human pathogen.