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

Autor:	Turner AG; School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia 4072, Australia., Djoko KY; School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia 4072, Australia.; Department of Biosciences, Durham University, Durham DH1 3LE, U.K., Ong CY; School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia 4072, Australia.; Australian Infectious Diseases Research Centre, The University of Queensland, St Lucia 4072, Australia., Barnett TC; Telethon Kids Institute, The University of Western Australia, Nedlands 6009, Australia., Walker MJ; School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia 4072, Australia mcewan@uq.edu.au mark.walker@uq.edu.au.; Australian Infectious Diseases Research Centre, The University of Queensland, St Lucia 4072, Australia., McEwan AG; School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia 4072, Australia mcewan@uq.edu.au mark.walker@uq.edu.au.; Australian Infectious Diseases Research Centre, The University of Queensland, St Lucia 4072, Australia.
Jazyk:	angličtina
Zdroj:	The Biochemical journal [Biochem J] 2019 Feb 14; Vol. 476 (3), pp. 595-611. Date of Electronic Publication: 2019 Feb 14.
DOI:	10.1042/BCJ20180902
Abstrakt:	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. (© 2019 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)
Databáze:	MEDLINE
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