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Bioengineering 2016, 3(1), 9; doi:10.3390/bioengineering3010009

Construction and Experimental Validation of a Quantitative Kinetic Model of Nitric Oxide Stress in Enterohemorrhagic Escherichia coli O157:H7

Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ 08544, USA
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Received: 21 November 2015 / Accepted: 1 February 2016 / Published: 6 February 2016
(This article belongs to the Special Issue Metabolic Engineering)
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Abstract

Enterohemorrhagic Escherichia coli (EHEC) are responsible for large outbreaks of hemorrhagic colitis, which can progress to life-threatening hemolytic uremic syndrome (HUS) due to the release of Shiga-like toxins (Stx). The presence of a functional nitric oxide (NO·) reductase (NorV), which protects EHEC from NO· produced by immune cells, was previously found to correlate with high HUS incidence, and it was shown that NorV activity enabled prolonged EHEC survival and increased Stx production within macrophages. To enable quantitative study of EHEC NO· defenses and facilitate the development of NO·-potentiating therapeutics, we translated an existing kinetic model of the E. coli K-12 NO· response to an EHEC O157:H7 strain. To do this, we trained uncertain model parameters on measurements of [NO·] and [O2] in EHEC cultures, assessed parametric and prediction uncertainty with the use of a Markov chain Monte Carlo approach, and confirmed the predictive accuracy of the model with experimental data from genetic mutants lacking NorV or Hmp (NO· dioxygenase). Collectively, these results establish a methodology for the translation of quantitative models of NO· stress in model organisms to pathogenic sub-species, which is a critical step toward the application of these models for the study of infectious disease. View Full-Text
Keywords: nitric oxide; enterohemorrhagic E. coli; kinetic model; ensemble modeling; Hmp; NorV; microaerobic; anaerobic nitric oxide; enterohemorrhagic E. coli; kinetic model; ensemble modeling; Hmp; NorV; microaerobic; anaerobic
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Robinson, J.L.; Brynildsen, M.P. Construction and Experimental Validation of a Quantitative Kinetic Model of Nitric Oxide Stress in Enterohemorrhagic Escherichia coli O157:H7. Bioengineering 2016, 3, 9.

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