Bacteria live in frequently changing environments and have to deal with a multitude of challenges. The chemical challenges to be faced are not only of exogenous origin, but can be the product of the metabolism, as in the case of methylglyoxal (MG), an endogenous electrophile that kills via damage to macromolecules. Escherichia coli (E. coli) has evolved sophisticated protective mechanisms to counteract the toxicity of MG. The glutathione-dependent glyoxalase system, consisting of glyoxalase I and II (GlxI & II), provides the main route for MG detoxification. Protection from MG is highly dependent on the activity of the KefB and KefC protein. KefB and KefC are homologous ligand-gated potassium efflux systems and are maintained inactive by the binding of glutathione, and are activated during MG detoxification by a specific intermediate molecule of the detoxification pathway, S-lactoylglutathione (SLG). The activity of these systems ultimately modulates the cytoplasmic pH. This study assessed the molecular and physiological role of the GlxII-encoding gene (gloB) in E. coli during MG stress. The study emphasises that the degree of KefB and KefC activation is affected by the relative specific activities of GlxI and GlxII via their impact on the SLG molecule. The significance of other genes in protection was poorly understood and this study allowed first insights into the transcriptional response of E. coli to MG stress. ChIPchip studies investigated the genome-wide RNA polymerase distribution of E. coli in response to MG. Furthermore, the contribution of the potassium efflux systems on transcriptional changes was assessed. The data show that E. coli invokes an adaptive transcriptional response that excludes the known key systems for cell survival. The data point to possible novel roles for several other mechanisms known to be involved for example aldehyde detoxification, potassium homeostasis and DNA damage repair.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:509209 |
| Date | January 2009 |
| Creators | Ozyamak, Ertan |
| Publisher | University of Aberdeen |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=59008 |
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