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

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

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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 (∼17mM) 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.

Original languageEnglish
Article number6418
JournalNature Communications
Volume6
DOIs
Publication statusPublished - 2015
Externally publishedYes

Bibliographical note

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 http://creativecommons.org/licenses/by/4.0/

Keywords

  • cadmium
  • metal-accumulation assays
  • homeostatis

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