A Chemical Biology Approach to Interrogate Quorum-Sensing Regulated Behaviors at the Molecular and Cellular Level

Abstract

SUMMARY Small molecule probes have been employed extensively to explore biological systems and elucidate cellular signaling pathways. In this study, we utilize an inhibitor of bacterial communication to monitor changes in the proteome of Salmonella enterica serovar Typhimurium with the aim of discovering new processes regulated by AI-2-based quorum sensing (QS), a mechanism of bacterial intracellular communication that allows for the coordination of gene expression in a cell density-dependent manner. In S. typhimurium, this system regulates the uptake and catabolism of intracellular signals and has been implicated in pathogenesis, including the invasion of host epithelial cells. We demonstrate that our QS antagonist is capable of selectively inhibiting the expression of known QS-regulated proteins in S. typhimurium, thus attesting that QS inhibitors may be used to confirm proposed and elucidate previously unidentified QS pathways without relying on genetic manipulation.

Metabolomic Analysis of the Effect of Lippia origanoides Essential Oil on the Inhibition of Quorum Sensing in Chromobacterium violaceum

“…Among these, EOs are promising antimicrobial natural products. They are volatile natural mixtures of compounds consisting mainly of terpenoid and phenolic compounds, distilled from different parts of the plant and exhibiting both antimicrobial and anti-QS activities [14][15][16]. In our previous study, a thymol-carvacrol chemotype Lippia origanoides EO (LOT-II) was a potent QS inhibitor against C. violaceum [17].…”

Glycation Reactivity of a Quorum‐Sensing Signaling Molecule

“…These results open new avenues toward tracking and understanding the fate and function of the elusive quorumsensing signaling molecule.Over the past decade,o ur group and others have investigated the bacterial biochemical properties of (4S)-4,5dihydroxy-2,3-pentanedione (DPD). [1] Our interest in this molecule originally stemmed from its distinct densely oxygenated five-carbon-atom makeup,a nd reports touting its ability to coordinate gene expression in both gram-negative and gram-positive bacteria in ap opulation-dependent manner,t ermed as autoinducer-2 quorum sensing (AI-2 QS). Moreover,w eh ave shown that DPD can exist in ac omplex, multispecies equilibrium whereby its unique architecture allows it to undergo cyclization and ring-opening reactions in as imilar fashion as do saccharides (Scheme 1A).…”