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

Begg, Stephanie; Eijkelkamp, Bart A.; Luo, Zhenyao; Counago, Rafael M; Morey, Jacqueline R; Maher, Megan J.; Ong, Cheryl-lynn Y.; McEwan, Alastair G.; Kobe, Bostjan; O'Mara, Megan; Paton, James C.; McDevitt, Christopher A

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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...[Show more]

dc.contributor.authorBegg, Stephanie
dc.contributor.authorEijkelkamp, Bart A.
dc.contributor.authorLuo, Zhenyao
dc.contributor.authorCounago, Rafael M
dc.contributor.authorMorey, Jacqueline R
dc.contributor.authorMaher, Megan J.
dc.contributor.authorOng, Cheryl-lynn Y.
dc.contributor.authorMcEwan, Alastair G.
dc.contributor.authorKobe, Bostjan
dc.contributor.authorO'Mara, Megan
dc.contributor.authorPaton, James C.
dc.contributor.authorMcDevitt, Christopher A
dc.date.accessioned2016-02-24T22:41:56Z
dc.identifier.issn2041-1723
dc.identifier.urihttp://hdl.handle.net/1885/98868
dc.description.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 (∼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.
dc.publisherMacmillan Publishers Ltd
dc.rightsAuthor/s retain copyright
dc.sourceNature Communications
dc.titleDysregulation of transition metal ion homeostasis is the molecular basis for cadmium toxicity in Streptococcus pneumoniae
dc.typeJournal article
local.description.notesImported from ARIES
local.identifier.citationvolume6
dc.date.issued2015
local.identifier.absfor039904 - Organometallic Chemistry
local.identifier.ariespublicationU4217927xPUB837
local.type.statusPublished Version
local.contributor.affiliationBegg, Stephanie, The University of Adelaide
local.contributor.affiliationEijkelkamp, Bart A., The University of Adelaide
local.contributor.affiliationLuo, Zhenyao, University of Queensland
local.contributor.affiliationCounago, Rafael M, University of Queensland
local.contributor.affiliationMorey, Jacqueline R, The University of Adelaide
local.contributor.affiliationMaher, Megan J., La Trobe University
local.contributor.affiliationOng, Cheryl-lynn Y., University of Queensland
local.contributor.affiliationMcEwan, Alastair G., University of Queensland
local.contributor.affiliationKobe, Bostjan, University of Queensland
local.contributor.affiliationO'Mara, Megan, College of Physical and Mathematical Sciences, ANU
local.contributor.affiliationPaton, James C., The University of Adelaide
local.contributor.affiliationMcDevitt, Christopher A, University of Adelaide
local.bibliographicCitation.issue6418
local.bibliographicCitation.startpage1
local.bibliographicCitation.lastpage11
local.identifier.doi10.1038/ncomms7418
local.identifier.absseo970103 - Expanding Knowledge in the Chemical Sciences
dc.date.updated2016-02-24T10:45:55Z
local.identifier.scopusID2-s2.0-84924118265
dcterms.accessRightsOpen Access
CollectionsANU Research Publications

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