Manganese homeostasis in group A Streptococcus is critical for resistance to oxidative stress and virulence

Turner, Andrew G., Ong, Cheryl-lynn, Gillen, Christine M., Davies, Mark R., West, Nicholas P., McEwan, Alastair G. and Walker, Mark J. (2015) Manganese homeostasis in group A Streptococcus is critical for resistance to oxidative stress and virulence. mBio, 6 2: 1-10. doi:10.1128/mBio.00278-15


Author Turner, Andrew G.
Ong, Cheryl-lynn
Gillen, Christine M.
Davies, Mark R.
West, Nicholas P.
McEwan, Alastair G.
Walker, Mark J.
Title Manganese homeostasis in group A Streptococcus is critical for resistance to oxidative stress and virulence
Formatted title
Manganese homeostasis in group A Streptococcus is critical for resistance to oxidative stress and virulence
Journal name mBio   Check publisher's open access policy
ISSN 2150-7511
Publication date 2015-03-24
Year available 2015
Sub-type Article (original research)
DOI 10.1128/mBio.00278-15
Open Access Status DOI
Volume 6
Issue 2
Start page 1
End page 10
Total pages 10
Place of publication Washington, DC United States
Publisher American Society for Microbiology
Language eng
Formatted abstract
Streptococcus pyogenes (group A Streptococcus [GAS]) is an obligate human pathogen responsible for a spectrum of human disease states. Metallobiology of human pathogens is revealing the fundamental role of metals in both nutritional immunity leading to pathogen starvation and metal poisoning of pathogens by innate immune cells. Spy0980 (MntE) is a paralog of the GAS zinc efflux pump CzcD. Through use of an isogenic mntE deletion mutant in the GAS serotype M1T1 strain 5448, we have elucidated that MntE is a manganese-specific efflux pump required for GAS virulence. The 5448ΔmntE mutant had significantly lower survival following infection of human neutrophils than did the 5448 wild type and the complemented mutant (5448ΔmntE::mntE). Manganese homeostasis may provide protection against oxidative stress, explaining the observed ex vivo reduction in virulence. In the presence of manganese and hydrogen peroxide, 5448ΔmntE mutant exhibits significantly lower survival than wild-type 5448 and the complemented mutant. We hypothesize that MntE, by maintaining homeostatic control of cytoplasmic manganese, ensures that the peroxide response repressor PerR is optimally poised to respond to hydrogen peroxide stress. Creation of a 5448ΔmntEperR double mutant rescued the oxidative stress resistance of the double mutant to wild-type levels in the presence of manganese and hydrogen peroxide. This work elucidates the mechanism for manganese toxicity within GAS and the crucial role of manganese homeostasis in maintaining GAS virulence.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
School of Chemistry and Molecular Biosciences
 
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Created: Fri, 27 Mar 2015, 20:57:46 EST by Mrs Louise Nimwegen on behalf of School of Chemistry & Molecular Biosciences