A stochastic model of Escherichia coli AI-2 quorum signal circuit reveals alternative synthesis pathways.

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TitleA stochastic model of Escherichia coli AI-2 quorum signal circuit reveals alternative synthesis pathways.
Publication TypeJournal Article
Year of Publication2006
AuthorsLi, J, Wang, L, Hashimoto, Y, Tsao, C-Y, Wood, TK, Valdes, JJ, Zafiriou, E, Bentley, WE
JournalMol Syst Biol
Volume2
Pagination67
Date Published2006
ISSN1744-4292
KeywordsBacterial Physiological Phenomena, Bacterial Proteins, Cell-Free System, Computer Simulation, Escherichia coli, Escherichia coli Proteins, Gene Expression Regulation, Bacterial, Genome, Bacterial, Models, Biological, Signal Transduction, Stochastic Processes
Abstract

Quorum sensing (QS) is an important determinant of bacterial phenotype. Many cell functions are regulated by intricate and multimodal QS signal transduction processes. The LuxS/AI-2 QS system is highly conserved among Eubacteria and AI-2 is reported as a 'universal' signal molecule. To understand the hierarchical organization of AI-2 circuitry, a comprehensive approach incorporating stochastic simulations was developed. We investigated the synthesis, uptake, and regulation of AI-2, developed testable hypotheses, and made several discoveries: (1) the mRNA transcript and protein levels of AI-2 synthases, Pfs and LuxS, do not contribute to the dramatically increased level of AI-2 found when cells are grown in the presence of glucose; (2) a concomitant increase in metabolic flux through this synthesis pathway in the presence of glucose only partially accounts for this difference. We predict that 'high-flux' alternative pathways or additional biological steps are involved in AI-2 synthesis; and (3) experimental results validate this hypothesis. This work demonstrates the utility of linking cell physiology with systems-based stochastic models that can be assembled de novo with partial knowledge of biochemical pathways.

DOI10.1038/msb4100107
Alternate JournalMol. Syst. Biol.
PubMed ID17170762
PubMed Central IDPMC1762088