Skip to main content

Research Repository

Advanced Search

Antimicrobial Action of Copper Is Amplified via Inhibition of Heme Biosynthesis.

Djoko, Karrera Y.; McEwan, Alastair G.

Authors

Alastair G. McEwan



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.

Citation

Djoko, K. Y., & McEwan, A. G. (2013). Antimicrobial Action of Copper Is Amplified via Inhibition of Heme Biosynthesis. ACS Chemical Biology, 8(10), 2217-2223. https://doi.org/10.1021/cb4002443

Journal Article Type Article
Acceptance Date Jul 29, 2013
Online Publication Date Jul 29, 2013
Publication Date 2013-10
Deposit Date Sep 6, 2017
Journal ACS Chemical Biology
Print ISSN 1554-8929
Electronic ISSN 1554-8937
Publisher American Chemical Society
Peer Reviewed Peer Reviewed
Volume 8
Issue 10
Pages 2217-2223
DOI https://doi.org/10.1021/cb4002443