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

• Published in: Infection and Immunity 2006-09, Vol.74 (9), p.5132-5139
• Main Authors: Hanks, Tracey S, Liu, Mengyao, McClure, Michael J, Fukumura, Maki, Duffy, Angela, Lei, Benfang
• Format: Article
• Language: English
• Subjects: Animals; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Bacteriology; Biological and medical sciences; Biological Transport - genetics; Down-Regulation; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation, Bacterial; Heme - metabolism; Ion Transport - genetics; Iron - metabolism; Manganese - metabolism; Membrane Transport Proteins - genetics; Mice; Microbiology; Miscellaneous; Molecular Pathogenesis; Repressor Proteins - genetics; Repressor Proteins - metabolism; Sequence Deletion; Streptococcal Infections - microbiology; Streptococcus; Streptococcus pyogenes - genetics; Streptococcus pyogenes - metabolism; Streptococcus pyogenes - pathogenicity; Transcription Factors - genetics; Transcription Factors - metabolism; Transcription, Genetic; Virulence - genetics
• ISSN: 0019-9567; 1098-5522
• DOI: 10.1128/IAI.00176-06

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.