Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/86632
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Type: Journal article
Title: Extracellular zinc competitively inhibits manganese uptake and compromises oxidative stress management in Streptococcus pneumoniae
Author: Eijkelkamp, B.
Morey, J.
Ween, M.
Ong, C.
McEwan, A.
Paton, J.
McDevitt, C.
Citation: PLoS One, 2014; 9(2):e89427-1-e89427-11
Publisher: Public Library of Science
Issue Date: 2014
ISSN: 1932-6203
1932-6203
Statement of
Responsibility: 
Bart A. Eijkelkamp, Jacqueline R. Morey, Miranda P. Ween, Cheryl-lynn Y. Ong, Alastair G. McEwan, James C. Paton, Christopher A. McDevitt
Abstract: Streptococcus pneumoniae requires manganese for colonization of the human host, but the underlying molecular basis for this requirement has not been elucidated. Recently, it was shown that zinc could compromise manganese uptake and that zinc levels increased during infection by S. pneumoniae in all the niches that it colonized. Here we show, by quantitative means, that extracellular zinc acts in a dose dependent manner to competitively inhibit manganese uptake by S. pneumoniae, with an EC50 of 30.2 µM for zinc in cation-defined media. By exploiting the ability to directly manipulate S. pneumoniae accumulation of manganese, we analyzed the connection between manganese and superoxide dismutase (SodA), a primary source of protection for S. pneumoniae against oxidative stress. We show that manganese starvation led to a decrease in sodA transcription indicating that expression of sodA was regulated through an unknown manganese responsive pathway. Intriguingly, examination of recombinant SodA revealed that the enzyme was potentially a cambialistic superoxide dismutase with an iron/manganese cofactor. SodA was also shown to provide the majority of protection against oxidative stress as a S. pneumoniae ΔsodA mutant strain was found to be hypersensitive to oxidative stress, despite having wild-type manganese levels, indicating that the metal ion alone was not sufficiently protective. Collectively, these results provide a quantitative assessment of the competitive effect of zinc upon manganese uptake and provide a molecular basis for how extracellular zinc exerts a ‘toxic’ effect on bacterial pathogens, such as S. pneumoniae.
Keywords: Extracellular Space; Streptococcus pneumoniae; Manganese; Zinc; Superoxide Dismutase; DNA Primers; Reverse Transcriptase Polymerase Chain Reaction; Sequence Analysis, DNA; Gene Expression Regulation, Enzymologic; Binding, Competitive; Oxidative Stress; Real-Time Polymerase Chain Reaction
Rights: © 2014 Eijkelkamp et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
RMID: 0020136393
DOI: 10.1371/journal.pone.0089427
Grant ID: http://purl.org/au-research/grants/arc/DP0986578
http://purl.org/au-research/grants/arc/DP120103957
http://purl.org/au-research/grants/nhmrc/1022240
http://purl.org/au-research/grants/nhmrc/565526
Appears in Collections:Molecular and Biomedical Science publications

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