EXPLORING INTERACTIONS BETWEEN THE NITRIC OXIDE AND HYDROGEN PEROXIDE RESPONSE NETWORKS OF ESCHERICHIA COLI

Abstract

This paper details the construction of a quantitative, kinetic model that accounts for interactions between the nitric oxide (NO.) and hydrogen peroxide (H\(_{2}\)O\(_{2}\)) stress response networks in Escherichia coli MG1655 cells. The model is trained on data of individual NO. clearance, individual H\(_{2}\)O\(_{2}\) clearance, and simultaneous NO. and H\(_{2}\)O\(_{2}\) clearance following treatment with the NO. donor DPTA, treatment withH\(_{2}\)O\(_{2}\), and co-treatment with both DPTA and H\(_{2}\)O\(_{2}\), respectively. Co-treatment led to a decrease in the NO. and H\(_{2}\)O\(_{2}\) clearance rates observed during individual treatments and caused cell death, which was not observed for individual treatments. Cell death currently stands as the major impediment to this project since the kinetic model assumes a constant cell density in all simulations. Once we determine co-treatment conditions that do not result in cell death, we can further optimize the model and perform additional experiments that will help us elucidate which interactions in the E. coli oxidative and nitrosative stress response networks are physiologically significant. It is our hope that this model can serve as a framework for future models that simulate the introduction of NO. and H\(_{2}\)O\(_{2}\) from the phagosomal environment into the bacterial cell and allow us to draw conclusions about the combined effect of these stressors on pathogenic bacterial stress response networks. A further understanding of these networks may aid in the development of novel antimicrobial techniques that rely on the synergistic effect of multiple oxidative and nitrosative stressors, such as NO. and H\(_{2}\)O\(_{2}\).