Open AccessA stochastic model of Escherichia coli AI‐2 quorum signal circuit reveals alternative synthesis pathways
Author(s) -
Li Jun,
Wang Liang,
Hashimoto Yoshifumi,
Tsao ChenYu,
Wood Thomas K,
Valdes James J,
Zafiriou Evanghelos,
Bentley William E
Publication year - 2006
Publication title -
molecular systems biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.523
H-Index - 148
ISSN - 1744-4292
DOI - 10.1038/msb4100107
Subject(s) - quorum sensing , biology , signal transduction , computational biology , metabolic pathway , systems biology , flux (metallurgy) , synthetic biology , phenotype , cell signaling , biochemistry , microbiology and biotechnology , gene , chemistry , virulence , organic chemistry
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.