Altering the communication networks of multispecies microbial systems using a diverse toolbox of AI-2 analogues.

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TitleAltering the communication networks of multispecies microbial systems using a diverse toolbox of AI-2 analogues.
Publication TypeJournal Article
Year of Publication2012
AuthorsGamby, S, Roy, V, Guo, M, Smith, JAI, Wang, J, Stewart, JE, Wang, X, Bentley, WE, Sintim, HO
JournalACS Chem Biol
Volume7
Issue6
Pagination1023-30
Date Published2012 Jun 15
ISSN1554-8937
Keywordsbeta-Galactosidase, Escherichia coli, Escherichia coli Proteins, Homoserine, Lactones, Phosphotransferases (Alcohol Group Acceptor), Pseudomonas aeruginosa, Quorum Sensing, Repressor Proteins, Salmonella typhimurium, Signal Transduction
Abstract

There have been intensive efforts to find small molecule antagonists for bacterial quorum sensing (QS) mediated by the "universal" QS autoinducer, AI-2. Previous work has shown that linear and branched acyl analogues of AI-2 can selectively modulate AI-2 signaling in bacteria. Additionally, LsrK-dependent phosphorylated analogues have been implicated as the active inhibitory form against AI-2 signaling. We used these observations to synthesize an expanded and diverse array of AI-2 analogues, which included aromatic as well as cyclic C-1-alkyl analogues. Species-specific analogues that disrupted AI-2 signaling in Escherichia coli and Salmonella typhimurium were identified. Similarly, analogues that disrupted QS behaviors in Pseudomonas aeruginosa were found. Moreover, we observed a strong correlation between LsrK-dependent phosphorylation of these acyl analogues and their ability to suppress QS. Significantly, we demonstrate that these analogues can selectively antagonize QS in single bacterial strains in a physiologically relevant polymicrobial culture.

DOI10.1021/cb200524y
Alternate JournalACS Chem. Biol.
PubMed ID22433054