Antimicrobial action of copper is amplified via inhibition of heme biosynthesis

Djoko, Karrera Y. and McEwan, Alastair G. (2013) Antimicrobial action of copper is amplified via inhibition of heme biosynthesis. ACS Chemical Biology, 8 10: 2217-2223. doi:10.1021/cb4002443

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Author Djoko, Karrera Y.
McEwan, Alastair G.
Title Antimicrobial action of copper is amplified via inhibition of heme biosynthesis
Formatted title
Antimicrobial action of copper is amplified via inhibition of heme biosynthesis
Journal name ACS Chemical Biology   Check publisher's open access policy
ISSN 1554-8929
1554-8937
Publication date 2013-10-18
Sub-type Article (original research)
DOI 10.1021/cb4002443
Open Access Status File (Author Post-print)
Volume 8
Issue 10
Start page 2217
End page 2223
Total pages 7
Place of publication Washington, DC, United States
Publisher American Chemical Society
Collection year 2014
Language eng
Formatted abstract
Copper (Cu) is a potent antimicrobial agent. Its use as a disinfectant goes back to antiquity, but this metal ion has recently emerged to have a physiological role in the host innate immune response. Recent studies have identified iron–sulfur containing proteins as key targets for inhibition by Cu. However, the way in these effects at the molecular level translate into a global effect on cell physiology is not fully understood. Here, we provide a new insight into the way in which Cu poisons bacteria. Using a copA mutant of the obligate human pathogen Neisseria gonorrhoeae that lacks a Cu efflux pump, we showed that Cu overloading led to an increased sensitivity to hydrogen peroxide. However, instead of promoting disproportionation of H2O2 via Fenton chemistry, Cu treatment led to an increased lifetime of H2O2 in cultures as a result of a marked decrease in catalase activity. We showed that this observation correlated with a loss of intracellular heme. We further established that Cu inhibited the pathway for heme biosynthesis. We proposed that this impaired ability to produce heme during Cu stress would lead to the failure to activate hemoproteins that participate in key processes, such as the detoxification of various reactive oxygen and nitrogen species, and aerobic respiration. The impact would be a global disruption of cellular biochemistry and an amplified Cu toxicity.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Chemistry and Molecular Biosciences
 
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Citation counts: TR Web of Science Citation Count  Cited 13 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 13 times in Scopus Article | Citations
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Created: Wed, 23 Oct 2013, 16:48:21 EST by Karrera Djoko on behalf of School of Chemistry & Molecular Biosciences