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.

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.-L. 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
• Public URL: https://durham-repository.worktribe.com/output/1306755