Mathematical Model of Iron Regulatory Mechanisms: Oxidant and Ferric Stress Modulation of Bacterial Growth and Survival in Escherichia coli

Understanding the regulatory mechanisms of metabolic drivers of bacterial growth, survival and activity is central to deconvolving intricate communal interactions which have far reaching implications. The iron regulatory network has been studied and mapped extensively having been implicated in its many roles in several biological processes involving cross-species interactions including biofilm development and microbiome composition and diversity (Seo, S.W et al. Nat. Communications, Sept. 2014; Yilmaz, B., & Li, H. Pharmaceuticals, Oct. 2018)

Here we build on and expand a mathematical model of genetic regulation of iron in E. coli (Semsey, S. et al. Nucleic acids research, Sept. 2006; Aashard A. & May, E. E. Unpublished) to accommodate modulatory effects of iron and oxidative stress on bacterial growth and survival. The expanded model simulates the effects of ferrous and ferric iron availability and hydrogen peroxide stress on bacterial survival and growth and compares the simulated response patterns of E. coli to experimental results from our empirical multi-stress model (Rasaputra et al. Unpublished).

We found from our simulation results that E. coli cells behave in precise distinct patterns in response to oxidant or ferric stress concordant with experimental results. We also report a perceived double negative survival reinforcement mechanism in response to both oxidant and ferric stress as opposed to singular stress points of either stress condition. Based on our results, we continue to expand our modeling studies of intracellular mechanisms of iron modulation for use in broader models, in particular our agent based model of E. coli biofilm formation (Latif, M., & May, E. E. Bulletin of mathematical biology, Sept. 2018), to probe and inform biological processes involving iron and its role in bacterial cells and communities.