Extracellular zinc competitively inhibits manganese uptake and compromises oxidative stress management in streptococcus pneumoniae

Eijkelkamp, Bart A., Morey, Jacqueline R., Ween, Miranda P., Ong, Cheryl-lynn Y., McEwan, Alastair G., Paton, James C. and McDevitt, Christopher A. (2014) Extracellular zinc competitively inhibits manganese uptake and compromises oxidative stress management in streptococcus pneumoniae. PLoS One, 9 2: . doi:10.1371/journal.pone.0089427


Author Eijkelkamp, Bart A.
Morey, Jacqueline R.
Ween, Miranda P.
Ong, Cheryl-lynn Y.
McEwan, Alastair G.
Paton, James C.
McDevitt, Christopher A.
Title Extracellular zinc competitively inhibits manganese uptake and compromises oxidative stress management in streptococcus pneumoniae
Formatted title
Extracellular zinc competitively inhibits manganese uptake and compromises oxidative stress management in streptococcus pneumoniae
Journal name PLoS One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2014-02-18
Year available 2014
Sub-type Article (original research)
DOI 10.1371/journal.pone.0089427
Open Access Status DOI
Volume 9
Issue 2
Total pages 11
Place of publication San Francisco, United States
Publisher Public Library of Science
Language eng
Formatted 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.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Article # e89427

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
School of Chemistry and Molecular Biosciences
Institute for Molecular Bioscience - Publications
 
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Created: Fri, 21 Feb 2014, 19:34:21 EST by Mrs Louise Nimwegen on behalf of School of Chemistry & Molecular Biosciences