The Mechanism of Copper Toxicity in Escherichia Coli

The goal of this study was to determine the mechanism of copper toxicity. Copper is toxic to both eukaryotes and prokaryotes and is the causative agent of Indian childhood cirrhosis, Tyrolean infantile cirrhosis, and Wilson disease. Studies in eukaryotic systems demonstrated that copper-toxified cells had elevated levels of DNA damage and oxidative stress. Therefore, the mechanism of copper toxicity was hypothesized to be mediated by oxidative DNA damage through a Fenton-like reaction. In contrast to this hypothesis, copper-stressed Escherichia coli sustained less oxidative DNA damage than unsupplemented cells. The levels of hydroxyl radical formation between copper-stressed and unsupplemented cells were similar, demonstrating that copper did not prevent iron-mediated oxidative DNA damage by blocking the Fenton reaction. Therefore, hydroxyl radicals must be formed away from the DNA. We hypothesize that copper-stress leads to the removal of iron from the DNA. The mechanism by which copper-stress causes iron to be displaced from the DNA is unknown. This study demonstrated that copper-mediated oxidative DNA damage does not occur and therefore cannot be the primary mechanism of copper toxicity.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Microbiology

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2014

Author dc:creator

• Macomber, Lee Emmett

Contributors dc:contributor

• Imlay, James A.

• Biology, Microbiology

Identifier

(UMI)AAI3363029

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/72515