Quorum quenching analysis in Pseudomonas aeruginosa and Escherichia coli: network topology and inhibition mechanism effect on the optimized inhibitor dose.
The discovery of quorum sensing as a mechanism for regulating specific phenotypes in bacteria based on population density has conveyed attention to find molecules capable of interfering quorum sensing networks (QSN) in a process coined quorum quenching. Here, we examined the dynamics of Escherichia coli AI-2 and Pseudomonas aeruginosa QSN exposed to signal degraders or competitors for binding transcriptional regulators. Stability analysis was performed for E. coli and P. aeruginosa finding no multistability in E. coli. However, our model allowed to discern that quenchers influence P. aeruginosa QSN multistability by reducing the interval of the amount of molecules of the extracellular signal that originate several steady states. We proposed a simulated annealing algorithm to optimize the quencher dose based on stochastic kinetics. E. coli QSN requires around 640 while P. aeruginosa QSN needs 253 quencher molecules per microorganism. This dose was found to be negatively influenced by the quencher-signal affinity.
Barrios
Andrés Fernando González
AF
Grupo de diseño de productos y procesos, Department of Chemical Engineering, Universidad de los Andes, Carrera 1 feminine No. 19 feminine40, Bogotá, Colombia. andgonza@uniandes.edu.co
Covo
Virginia
V
Medina
Luis Miguel
LM
Vives-Florez
Martha
M
Achenie
Luke
L
D000465:Algorithms; D001426:Bacterial Proteins / Q000502:physiology; D001698:Biomedical Engineering; D013437:Carbon-Sulfur Lyases / Q000502:physiology; D004926:Escherichia coli / Q000502:physiology*; D029968:Escherichia coli Proteins / Q000502:physiology; D006714:Homoserine / Q000031:analogs & derivatives / Q000502:physiology; D007700:Kinetics; D007783:Lactones; D008954:Models, Biological; D011550:Pseudomonas aeruginosa / Q000502:physiology*; D053038:Quorum Sensing / Q000502:physiology*; D015398:Signal Transduction; D013269:Stochastic Processes
D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D007783:Lactones; C091088:N-octanoylhomoserine lactone; D006714:Homoserine; D013437:Carbon-Sulfur Lyases; C117753:LuxS protein, Bacteria