104092-73-1Relevant articles and documents
Synthetic analogs tailor native AI-2 signaling across bacterial species
Roy, Varnika,Smith, Jacqueline A. I.,Wang, Jingxin,Stewart, Jessica E.,Bentley, William E.,Sintim, Herman O.
, p. 11141 - 11150 (2010)
The widespread use of antibiotics and the emergence of resistant strains call for new approaches to treat bacterial infection. Bacterial cell-cell communication or quorum sensing (QS) is mediated by signatures of small molecules that represent targets for quenching communication and avoiding virulent phenotypes. Only a handful of small molecules that antagonize the action of the universal autoinducer, AI-2, have been reported. The biological basis of antagonism, as well as the targets for these select few AI-2 antagonists, have not been clearly defined. We have developed C-1 alkyl analogs of AI-2 that quench the QS response in multiple bacterial species simultaneously. We also demonstrate the biological basis for this action. Like AI-2, the analogs are activated by the bacterial kinase, LsrK, and modulate AI-2 specific gene transcription through the transcriptional regulator, LsrR. Interestingly, addition of a single carbon to the C1-alkyl chain of the analog plays a crucial role in determining the effect of the analog on the QS response. While an ethyl modified analog is an agonist, propyl becomes an antagonist of the QS circuit. In a trispecies synthetic ecosystem comprised of E. coli, S. typhimurium, and V. harveyi we discovered both cross-species and species-specific anti-AI-2 QS activities. Our results suggest entirely new modalities for interrupting or tailoring the network of communication among bacteria.
