For example, the production of homoserine lactonases or acylases by Bacillus or Pseudomonas has been selleck chemicals Volasertib shown to lead to the destruction of autoinducers Inhibitors,Modulators,Libraries (homoserine lactones) produced by competing bacteria [11]. Also, small molecules or autoinducers produced by some bacteria or hosts have been shown to disrupt the quorum sensing of others [12�C14].Several groups have been interested in the development of small molecules that could be used to inhibit autoinducer signaling in a variety of bacteria [15�C22]. Most of these small molecules have been derivatives of the natural quorum sensing molecules. For example Sugar [22], Blackwell [23] and others [24,25] have demonstrated that modifications of the species specific homoserine autoinducer, called AI-1, afford analogs that could compete with the native signaling molecule.
The Janda [19,26,27] and the Sintim [20,28] Inhibitors,Modulators,Libraries groups have focused on analogs of the universal quorum sensing molecule, AI-2. AI-2 is termed universal because it is either produced or sensed by over seventy different bacterial species. Analogs of AI-2 have been shown to either act as synergistic agonists in some Vibrio species [26,28] or antagonist [20] in enteric bacteria, such as E. coli and S. typhimurium. Interestingly, it has been demonstrated that the nature of the C1 acyl group in AI-2 analogs confers specificity in disrupting QS processes in a variety of bacteria [20]. For example, hexyl-DPD (an analog of AI-2, which has the C1 methyl group in the native compound replaced by a hexyl group) inhibits AI-2-mediated lsr expression in E.
coli whereas this same molecule Inhibitors,Modulators,Libraries is ineffective against AI-2-mediated lsr expression in the analogous enteric bacteria, S. typhimurium. On the other hand, isobutyl DPD (for this analog, the methyl group is replaced with the isobutyl group) Inhibitors,Modulators,Libraries could inhibit AI-2-mediated lsr expression in S. typhimurium, implying that subtle differences in the C1 substituents of AI-2 could result in significant differences in biological response [20].One of the limitations of the use of AI-2 analogs in selectively modulating bacterial behavior is the instability of these analogs. At high concentrations, it has been shown that AI-2 form dimers (see Figure 1), which are not biologically active [29]. This makes the purification of AI-2 or analogs on silica gel problematic and most studies that use synthetic AI-2 use unpurified molecules.
Others have attempted to solve the instability issue associated with AI-2 by making Batimastat ester derivatives that hydrolyze in vivo to release active autoinducers [30]. This strategy is promising in delivering purer and more stable AI-2 analogs that could be used in studying bacterial communication, with implications for disease control or synthetic biology applications. However, detailed study that correlates the nature of the ester group on AI-2 and biological activity sellekchem has not been described.