(485aa) Rational Design of Quorum Sensing Inhibitors: The Case of Indole in Escherichia Coli

1. Grupo de Diseño de Productos y Procesos (GDPP), Department of Chemical Engineering, Universidad de los Andes Carrera 1E No. 19 A -40, Bogotá, Colombia

Previous studies have shown that indole is a sign of quorum sensing in Escherichia coli (E. coli) and other bacteria [1]. In the case of E coli, this signal negatively regulates biofilm formation [2]. This phenotype provides certain advantages such as resistance to antibiotics. The aim of this work was to find potential inhibitors of the indole signal, having as a start up framework Pseudomonas putida (P. putida) indole oxidases. Molecular docking was carried out for different in silico mutations in the enzyme in order to determine the binding energy using Autodock 4.0 and consequently the enzyme with the best ability to degrade the signal. Once the amino acids are mutated, the geometric structure of the enzyme is optimized by molecular mechanics using AMBER as a force field. After the tertiary structure has been determined, the binding energy was determined and mutations were selected to allow the lowest energy. Finally, we performed molecular dynamics simulations using verlet algorithm for the purpose of evaluate the stability of the mutations. The enzyme that was chosen to perform the mutations, had a initially binding energy with the indol of -9,98 kcal/mol. We replace the ASN 201, ASP 205 and ASN 297 for ALA 201, LEU 205 and LEU 297 respectively. This change improved the binding energy to -41,65kcal/mol.

[1]Lee, J., Jayaraman, A., & Wood, T. (2007). Indole is an inter-species biofilm signal mediated by SdiA . BMC Microbiology , 1-15.

[2]Wang, D., Ding, X., & Rather, P. (2001). Indole can act as an Extracelluar Singal in Escherichia coli. Journal of Bacteriology , 4210-4216.