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Infection and Immunity, May 2003, p. 2656-2664, Vol. 71, No. 5
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.5.2656-2664.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

MtsABC Is Important for Manganese and Iron Transport, Oxidative Stress Resistance, and Virulence of Streptococcus pyogenes

Robert Janulczyk,* Susanna Ricci,{dagger} and Lars Björck

Section for Molecular Pathogenesis, Department of Cell and Molecular Biology, BMC, University of Lund, 221 84 Lund, Sweden

Received 12 July 2002/ Returned for modification 23 September 2002/ Accepted 19 December 2002

MtsABC is a Streptococcus pyogenes ABC transporter which was previously shown to be involved in iron and zinc accumulation. In this study, we showed that an mtsABC mutant has impaired growth, particularly in a metal-depleted medium and an aerobic environment. In metal-depleted medium, growth was restored by the addition of 10 µM MnCl2, whereas other metals had modest or no effect. A characterization of metal radioisotope accumulation showed that manganese competes with iron accumulation in a dose-dependent manner. Conversely, iron competes with manganese accumulation but to a lesser extent. The mutant showed a pronounced reduction (>90%) of 54Mn accumulation, showing that MtsABC is also involved in Mn transport. Using paraquat and hydrogen peroxide to induce oxidative stress, we show that the mutant has an increased susceptibility to reactive oxygen species. Moreover, activity of the manganese-cofactored superoxide dismutase in the mutant is reduced, probably as a consequence of reduced intracellular availability of manganese. The enzyme functionality was restored by manganese supplementation during growth. The mutant was also attenuated in virulence, as shown in animal experiments. These results emphasize the role of MtsABC and trace metals, especially manganese, for S. pyogenes growth, susceptibility to oxidative stress, and virulence.


* Corresponding author. Mailing address: Section for Molecular Pathogenesis, Department of Cell and Molecular Biology, BMC, University of Lund, Tornavägen 10, 221 84 Lund, Sweden. Phone: 46 46 224489. Fax: 46 46 157756. E-mail: Robert.Janulczyk{at}medkem.lu.se.

Editor: V. J. DiRita

{dagger} Present address: Laboratory of Molecular Microbiology and Biotechnology, Section of Microbiology, Department of Molecular Biology, University of Siena, 53100 Siena, Italy.


Infection and Immunity, May 2003, p. 2656-2664, Vol. 71, No. 5
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.5.2656-2664.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.




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