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Biochem J. 2019 Feb 14;476(3):595-611. doi: 10.1042/BCJ20180902.

Group A Streptococcus co-ordinates manganese import and iron efflux in response to hydrogen peroxide stress.

Author information

1
School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia 4072, Australia.
2
Department of Biosciences, Durham University, Durham DH1 3LE, U.K.
3
Australian Infectious Diseases Research Centre, The University of Queensland, St Lucia 4072, Australia.
4
Telethon Kids Institute, The University of Western Australia, Nedlands 6009, Australia.
5
School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia 4072, Australia mcewan@uq.edu.au mark.walker@uq.edu.au.

Abstract

Bacterial pathogens encounter a variety of adverse physiological conditions during infection, including metal starvation, metal overload and oxidative stress. Here, we demonstrate that group A Streptococcus (GAS) utilises Mn(II) import via MtsABC during conditions of hydrogen peroxide stress to optimally metallate the superoxide dismutase, SodA, with Mn. MtsABC expression is controlled by the DtxR family metalloregulator MtsR, which also regulates the expression of Fe uptake systems in GAS. Our results indicate that the SodA in GAS requires Mn for full activity and has lower activity when it contains Fe. As a consequence, under conditions of hydrogen peroxide stress where Fe is elevated, we observed that the PerR-regulated Fe(II) efflux system PmtA was required to reduce intracellular Fe, thus protecting SodA from becoming mismetallated. Our findings demonstrate the co-ordinate action of MtsR-regulated Mn(II) import by MtsABC and PerR-regulated Fe(II) efflux by PmtA to ensure appropriate Mn(II) metallation of SodA for optimal superoxide dismutase function.

KEYWORDS:

Streptococcus pyogenes; iron; manganese; oxidative stress; superoxide dismutases

PMID:
30670571
DOI:
10.1042/BCJ20180902

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