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Infection and Immunity, September 2006, p. 5132-5139, Vol. 74, No. 9
0019-9567/06/$08.00+0     doi:10.1128/IAI.00176-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Differential Regulation of Iron- and Manganese-Specific MtsABC and Heme-Specific HtsABC Transporters by the Metalloregulator MtsR of Group A Streptococcus

Tracey S. Hanks, Mengyao Liu, Michael J. McClure, Maki Fukumura, Angela Duffy, and Benfang Lei*

Department of Veterinary Molecular Biology, Montana State University, Bozeman, Montana 59717

Received 1 February 2006/ Returned for modification 8 May 2006/ Accepted 19 June 2006

The genome of the human pathogen group A Streptococcus (GAS) encodes the transporters MtsABC, FtsABCD, and HtsABC to take up ferric and manganese ions, ferric ferrichrome, and heme, respectively. The GAS genome also encodes two metalloregulators PerR and MtsR. To understand the regulation of the expression of these transporters, the mtsR and perR deletion mutants of a GAS serotype M1 strain were generated, and the effects of the deletions and Fe3+, Mn2+, and Zn2+ on the expression of mtsA, htsA, and ftsB were examined. Mn2+ dramatically depresses mtsA transcription and levels of the MtsA protein but does not downregulate the expression of htsA and ftsB. Fe3+ decreases the expression of mtsA and htsA but has no effect on ftsB expression. Zn2+ has no effect on the expression of all three genes. The deletion of mtsR abolishes the Mn2+- and Fe3+-induced depression of mtsA expression and the Fe3+-dependent decrease in htsA expression. The deletion of mtsR does not significantly alter GAS virulence in a mouse model of subcutaneous infection. The deletion of perR does not affect the expression of the genes in response to the metal ions. MtsR binds to the mts promoter region in the presence of Mn2+ or Fe2+. The results indicate that MtsR differentially regulates the expression of mtsABC and htsABC.

* Corresponding author. Mailing address: Veterinary Molecular Biology, Montana State University, P.O. Box 173610, Bozeman, MT 59717. Phone: (406) 994-6389. Fax: (406) 994-4303. E-mail: blei{at}montana.edu.

Editor: F. C. Fang

Infection and Immunity, September 2006, p. 5132-5139, Vol. 74, No. 9
0019-9567/06/$08.00+0     doi:10.1128/IAI.00176-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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