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Cited by 29Bacterial Genetics and BiotechnologyRedox biology and oxidative stressStreptococcal Infections and Treatments

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

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Turner, Andrew G., Djoko, Karrera Y., Ong, Cheryl-lynn Y., Barnett, Timothy C., Walker, Mark J., McEwan, Alastair G.·2019·Biochemical Journal
DOI 10.1042/bcj20180902
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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.

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  • MnSOD can be metalated by iron, although this can lead to reduced activity and thereby increase cell sensitivity to oxidative stress.

    “MnSOD can also be metalated by iron, although this can lead to reduced activity and thereby increase cell sensitivity to oxidative stress.108”

    From Metals in Motion: Understanding Labile Metal Pools in Bacteria (2025) · cites this paper as [108]

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Authors
Turner, A. G., Djoko, K. Y., Ong, C.-L. Y., Barnett, T. C., Walker, M. J., & McEwan, A. G.
Affiliations
  • The University of Queensland (AU)
  • The Kids Research Institute Australia (AU)
Corresponding author
  • Walker, Mark J.
  • McEwan, Alastair G.
ORCID
Venue
Biochemical Journal
Publisher
Portland Press Ltd.
Published
2019-02-14
Volume
476
Issue
3
Pages
595-611
ISSN
  • 0264-6021 (ISSN-L)
  • 1470-8728
DOI
10.1042/bcj20180902
OpenAlex
W2911732276
Cited by
29
References
10
Citations by year
2026: 1 · 2025: 3 · 2024: 4 · 2023: 4 · 2022: 2 · 2021: 6 · 2020: 6 · 2019: 3
FWCI
2.56
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Biochemical Journal (publishedVersion)
  • PubMed (publishedVersion)
  • Durham Research Online (Durham University) (acceptedVersion)
  • Durham Research Online (Durham University) (submittedVersion, cc-by)
  • UWA Profiles and Research Repository (UWA) (submittedVersion)
Funders
National Health and Medical Research Council (1084460)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Streptococcal Infections and Treatments
Keywords
Streptococcus pyogenes, iron efflux, hydrogen peroxide stress, superoxide dismutase, soft drinks, PerR, metalloregulation, oxidative stress, metal homeostasis, iron absorption
MeSH terms
Bacterial Proteins, Hydrogen Peroxide, Iron, Manganese, Streptococcus pyogenes, Superoxide Dismutase, Oxidative Stress

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