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

• DOI: 10.1038/ncomms7418
• Publication Date: 2015-03-03T10:09:32Z
• Authors: 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. Mc...
• Keywords: Models, Molecular; 570; 550; 1300 Biochemistry; Protein Conformation; Lipoproteins; Immunoblotting; Genetics and Molecular Biology; Article; 03 medical and health sciences; Models; Homeostasis; 3100 Physics and Astronomy; Magnesium; cadmium toxicity; Adhesins, Bacterial; 0303 health sciences; Reverse Transcriptase Polymerase Chain Reaction; Bacterial; Molecular; 500; cadmium accumulation; 1600 Chemistry; Adhesins; 3. Good health; Multidisciplinary Sciences; Oxidative Stress; Zinc; Streptococcus pneumoniae; 13. Climate action; Science & Technology - Other Topics; Crystallization; Cadmium

AbstractCadmium 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.