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Simultaneous Measurement of Superoxide/Hydrogen Peroxide and NADH Production by Flavin-containing Mitochondrial Dehydrogenases
Published on: February 24, 2018
Group A Streptococcus co-ordinates manganese import and iron efflux in response to hydrogen peroxide stress
Andrew G Turner1, Karrera Y Djoko1,2, Cheryl-Lynn Y Ong1,3
1School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia 4072, Australia.
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.
Insights
Group A Streptococcus uses manganese import (MtsABC) and iron export (PmtA) to ensure its superoxide dismutase (SodA) is correctly activated with manganese, crucial for combating oxidative stress during infection.
Area of Science:
- Microbiology
- Bacterial Pathogenesis
- Oxidative Stress Response
Background:
- Bacterial pathogens face challenges like metal imbalance and oxidative stress during infection.
- Group A Streptococcus (GAS) must manage intracellular metal levels for survival and virulence.
Purpose of the Study:
- To investigate how GAS regulates manganese and iron homeostasis under oxidative stress.
- To elucidate the role of specific transporters and regulators in maintaining superoxide dismutase function.
Main Methods:
- Analysis of MtsABC manganese import system regulated by MtsR.
- Investigation of the PerR-regulated iron efflux system PmtA.
- Assessment of SodA activity under varying metal conditions and stress.
Main Results:
- GAS utilizes MtsABC for Mn(II) import under hydrogen peroxide stress.
- SodA requires manganese for optimal activity; iron incorporation reduces its function.
- PmtA is essential for reducing intracellular iron and preventing SodA "mismetallation" under high iron conditions.
Conclusions:
- MtsR-regulated Mn(II) import and PerR-regulated Fe(II) efflux work coordinately.
- This coordinated action ensures proper Mn(II) metallation of SodA for effective superoxide dismutase function in GAS.
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