451af E. Coli Autoinducer 2 Uptake Could Be Induced by Intracellular Factors Such as Luxs Rate but Not Necessarily by the Cell Density: Analysis of the Network Topology Using Bifurcation Analysis

Andres Fernando Gonzalez Barrios and Luke E. K. Achenie. Chemical Engineering, University of Connecticut, Dept. of Chemical Engineering, Unit 3222, 191 Auditorium Road, Storrs, CT 06269

Cross-species, quorum-sensing signal AI-2 uptake in E. coli was recently elucidated (J. Bacterio.,187:2066-2076) and it is known to be controlled by the lsr operon in a manner analogous to Salmonella Thyphimurium (Mol. Microbiol. 42:777-793). Previously, it has been found that this signal induces genes related to motility (Mol. Microbiol. 43:809-821), pathogenesis (J. Bacteriol.183: 5187-5197), and biofilm formation (J. Bacteriol.188: 305-316). Nevertheless, the AI-2 synthase, LuxS, is not directly or indirectly induced by the presence of the signal, differing from other prokaryotes such as Pseudomonas Aeruginosa whose signal synthases (LasI and RhlI) are positively induced by the autoinducer signal (J. Bacteriol. 179:3127-3132). This difference in the topology of the network raises questions regarding the actual role of the lsr operon and the factors that induce the network. Considering that this kind of cellular response implies a bistable, or hysteretic form of relationship between the signal concentration and the induction of several genes (Biosystems, In press), we modeled the lsr operon in E. coli and carried out a novel method in studying the dynamic quorum sensing network: bifurcation analysis. Indeed, it was found that the concentration of the signal is not the only factor that could switch the network but also LuxS rate. The increasing LuxS rate leads to a bifold bifurcation indicating different equilibrium points, and that the rate of LuxS induces the uptake process. Catabolic repression, which is known to influence uptake and synthesis of AI-2, also affects the stability of the network primarily through controlling luxS and the stress sigma factor, RpoS, which negatively regulates the lsr operon, does not play a big role in the stability of the Network. These results corroborate (Microbiol. 148: 909-922) that AI-2 may not play a role as a quorum sensing signal but as an indicator of the physiological state of the cell.