A theoretical interpretation of the transient sialic acid toxicity of a nanR mutant of Escherichia coli

Chu, Dominique and Roobol, J. and Blomfield, I.C. (2008) A theoretical interpretation of the transient sialic acid toxicity of a nanR mutant of Escherichia coli. Journal of Molecular Biology, 375 (3). pp. 875-889. ISSN 0022-2836 . (Access to this publication is restricted)

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http://dx.doi.org/10.1016/j.jmb.2007.10.073

Abstract

This article reports on experimental evidence that an Escherichia coli nanR mutant shows inhibited growth in N-acetylneuraminic acid. This effect is prevented when inocula are grown in an excess of glucose, but not in an excess of glycerol. The nanATEK operon is controlled by catabolite repression, suggesting that diminished expression of the nanATEK operon in the presence of glucose explains the inocula effects. Neither double nanR-nagC nor nanR dam mutants show growth inhibition in the presence of N-acetylneuraminic acid. A theoretical model of N-acetylneuraminic acid metabolism (i.e., in particular of the nanATEK and nagBACD operons) is presented; the model suggests an interpretation of this effect as being due to transient high accumulations of GlcNAc-6P in the cell. This accumulation would lead to suppression of central metabolic functions of the cell, thus causing inhibited growth. Based on the theoretical model and experimental data, it is hypothesised that the nanATEK operon is induced in a two-step mechanism. The first step is likely to be repressor displacement by N-acetylneuraminic acid. The second stage is hypothesised to involve Dam methylation to achieve full induction.

Item Type: Article
Additional information: 1089-8638 (Electronic) Journal Article Research Support, Non-U.S. Gov't
Uncontrolled keywords: Computer Simulation Escherichia coli/*genetics/metabolism Glucose/metabolism Kinetics Models, Biological *Models, Theoretical *Mutation N-Acetylneuraminic Acid/biosynthesis/genetics/metabolism/*toxicity Operon RNA, Messenger/metabolism Repressor Proteins/*genetics/metabolism
Subjects: Q Science
Divisions: Faculties > Science Technology and Medical Studies > School of Biosciences
Depositing User: Dominique Chu
Date Deposited: 13 Jan 2010 12:58
Last Modified: 03 Dec 2013 13:45
Resource URI: http://kar.kent.ac.uk/id/eprint/22674 (The current URI for this page, for reference purposes)
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