Dysregulation of transition metal ion homeostasis is the molecular basis for cadmium toxicity in Streptococcus pneumoniae

Begg, Stephanie L., Eijkelkamp, Bart A., Luo, Zhenyao, Couñago, Rafael M., Morey, Jacqueline R., Maher, Megan J., Ong, Cheryl-lynn Y., McEwan, Alastair G., Kobe, Bostjan, O'Mara, Megan L., Paton, James C. and McDevitt, Christopher A. (2015) Dysregulation of transition metal ion homeostasis is the molecular basis for cadmium toxicity in Streptococcus pneumoniae. Nature Communications, 6 6418: 1-11. doi:10.1038/ncomms7418


Author Begg, Stephanie L.
Eijkelkamp, Bart A.
Luo, Zhenyao
Couñago, Rafael M.
Morey, Jacqueline R.
Maher, Megan J.
Ong, Cheryl-lynn Y.
McEwan, Alastair G.
Kobe, Bostjan
O'Mara, Megan L.
Paton, James C.
McDevitt, Christopher A.
Title Dysregulation of transition metal ion homeostasis is the molecular basis for cadmium toxicity in Streptococcus pneumoniae
Formatted title
Dysregulation of transition metal ion homeostasis is the molecular basis for cadmium toxicity in Streptococcus pneumoniae
Journal name Nature Communications   Check publisher's open access policy
ISSN 2041-1723
Publication date 2015-03-03
Year available 2015
Sub-type Article (original research)
DOI 10.1038/ncomms7418
Open Access Status DOI
Volume 6
Issue 6418
Start page 1
End page 11
Total pages 11
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Collection year 2016
Language eng
Formatted 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.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

 
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Created: Fri, 06 Mar 2015, 13:00:47 EST by Mrs Louise Nimwegen on behalf of School of Chemistry & Molecular Biosciences