title: A stochastic model of Escherichia coli AI-2 quorum signal circuit reveals alternative synthesis pathways.
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.
authors.affiliation: Center for Biosystems Research, University of Maryland Biotechnology Institute, College Park, Maryland, MD, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: Liang
authors.initials: L
authors.lastname: Wang
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Hashimoto
authors.forename: Chen-Yu
authors.initials: CY
authors.lastname: Tsao
authors.forename: Thomas K
authors.initials: TK
authors.lastname: Wood
authors.forename: James J
authors.initials: JJ
authors.lastname: Valdes
authors.forename: Evanghelos
authors.initials: E
authors.lastname: Zafiriou
authors.forename: William E
authors.initials: WE
authors.lastname: Bentley
mesh_terms: D018407:Bacterial Physiological Phenomena; D001426:Bacterial Proteins / Q000737:chemistry; D002474:Cell-Free System; D003198:Computer Simulation; D004926:Escherichia coli / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000502:physiology; D015964:Gene Expression Regulation, Bacterial; D016680:Genome, Bacterial; D008954:Models, Biological; D015398:Signal Transduction; D013269:Stochastic Processes
chemical_list: D001426:Bacterial Proteins; D029968:Escherichia coli Proteins