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

Turner, Andrew G.; Djoko, Karrera Y.; Ong, Cheryl-lynn Y.; Barnett, Timothy C.; Walker, Mark J.; McEwan, Alastair G.

doi:10.1042/bcj20180902

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

Turner, Andrew G.; Djoko, Karrera Y.; Ong, Cheryl-lynn Y.; Barnett, Timothy C.; Walker, Mark J.; McEwan, Alastair G.

Authors

Andrew G. Turner

Dr Karrera Djoko karrera.djoko@durham.ac.uk
Associate Professor

Cheryl-lynn Y. Ong

Timothy C. Barnett

Mark J. Walker

Alastair G. McEwan

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) utilizes 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 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 coordinate 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.

Citation

Turner, A. G., Djoko, K. Y., Ong, C. Y., Barnett, T. C., Walker, M. J., & McEwan, A. G. (2019). Group A Streptococcus co-ordinates manganese import and iron efflux in response to hydrogen peroxide stress. Biochemical Journal, 476(3), 595-611. https://doi.org/10.1042/bcj20180902

Journal Article Type	Article
Acceptance Date	Jan 18, 2019
Publication Date	Feb 14, 2019
Deposit Date	Mar 5, 2019
Publicly Available Date	Feb 14, 2020
Journal	Biochemical Journal
Print ISSN	0264-6021
Electronic ISSN	1470-8728
Publisher	Portland Press
Peer Reviewed	Peer Reviewed
Volume	476
Issue	3
Pages	595-611
DOI	https://doi.org/10.1042/bcj20180902

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Copyright Statement
This research was originally published in Turner, Andrew G., Djoko, Karrera Y., Ong, Cheryl-lynn Y., Barnett, Timothy C., Walker, Mark J. & McEwan, Alastair G. (2019). Group A Streptococcus co-ordinates manganese import and iron efflux in response to hydrogen peroxide stress. Biochemical Journal 476(3): 595 © the Biochemical Society.