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Type: Journal article
Title: Dysregulation of transition metal ion homeostasis is the molecular basis for cadmium toxicity in Streptococcus pneumoniae
Author: Begg, S.
Eijkelkamp, B.
Luo, Z.
Couñago, R.
Morey, J.
Maher, M.
Ong, C.
McEwan, A.
Kobe, B.
O'Mara, M.
Paton, J.
McDevitt, C.
Citation: Nature Communications, 2015; 6(6418):6418-1-6418-11
Publisher: Nature Publishing Group
Issue Date: 2015
ISSN: 2041-1723
Statement of
Stephanie L. Begg, Bart A. Eijkelkamp, Zhenyao Luo, Rafael M. Couñago, Jacqueline R. Morey, Megan J. Maher, Cheryl-lynn Y. Ong, Alastair G. McEwan, Bostjan Kobe, Megan L. O, Mara, James C. Paton, Christopher A. McDevitt
Abstract: Cadmium is a transition metal ion that is highly toxic in biological systems. Although relatively rare in the Earth's crust, anthropogenic release of cadmium since industrialization has increased biogeochemical cycling and the abundance of the ion in the biosphere. Despite this, the molecular basis of its toxicity remains unclear. Here we combine metal-accumulation assays, high-resolution structural data and biochemical analyses to show that cadmium toxicity, in Streptococcus pneumoniae, occurs via perturbation of first row transition metal ion homeostasis. We show that cadmium uptake reduces the millimolar cellular accumulation of manganese and zinc, and thereby increases sensitivity to oxidative stress. Despite this, high cellular concentrations of cadmium (~17 mM) are tolerated, with negligible impact on growth or sensitivity to oxidative stress, when manganese and glutathione are abundant. Collectively, this work provides insight into the molecular basis of cadmium toxicity in prokaryotes, and the connection between cadmium accumulation and oxidative stress.
Keywords: Streptococcus pneumoniae; Magnesium; Cadmium; Zinc; Lipoproteins; Adhesins, Bacterial; Immunoblotting; Crystallization; Reverse Transcriptase Polymerase Chain Reaction; Protein Conformation; Oxidative Stress; Homeostasis; Models, Molecular
Rights: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit
RMID: 0030023998
DOI: 10.1038/ncomms7418
Appears in Collections:Molecular and Biomedical Science publications

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