A stochastic model of Escherichia coli AI-2 quorum signal circuit reveals alternative synthesis pathways.
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.
Li
Jun
J
Center for Biosystems Research, University of Maryland Biotechnology Institute, College Park, Maryland, MD, USA.
Wang
Liang
L
Hashimoto
Yoshifumi
Y
Tsao
Chen-Yu
CY
Wood
Thomas K
TK
Valdes
James J
JJ
Zafiriou
Evanghelos
E
Bentley
William E
WE
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
D001426:Bacterial Proteins; D029968:Escherichia coli Proteins