PMID:12183543

Citation	Ricci, S, Janulczyk, R and Björck, L (2002) The regulator PerR is involved in oxidative stress response and iron homeostasis and is necessary for full virulence of Streptococcus pyogenes. Infect. Immun. 70:4968-76
Abstract	Ferric uptake regulator (Fur) and Fur-like proteins form an important family of transcriptional regulators in many bacterial species. In this work we have characterized a Fur-like protein, the peroxide regulator PerR, in an M1 serotype of Streptococcus pyogenes. To determine the role of PerR in S. pyogenes, we inactivated the gene by allelic replacement. PerR-deficient bacteria showed 48% reduction of (55)Fe incorporation from the culture medium. Transcriptional analysis revealed that mtsA, encoding a metal-binding protein of an ABC transporter in S. pyogenes, was transcribed at lower levels than were wild-type cells. Although total iron accumulation was reduced, the growth of the mutant strain was not significantly hampered. The mutant showed hyperresistance to hydrogen peroxide, and this response was induced in wild-type cells by growth in aerobiosis, suggesting that PerR acts as an oxidative stress-responsive repressor. PerR may also participate in the response to superoxide stress, as the perR mutant was more sensitive to the superoxide anion and had a reduced transcription of sodA, which encodes the sole superoxide dismutase of S. pyogenes. Complementation of the mutation with a functional perR gene restored (55)Fe incorporation, response to peroxide stress, and transcription of both mtsA and sodA to levels comparable to those of wild-type bacteria. Finally, the perR mutant was attenuated in virulence in a murine air sac model of infection (P < 0.05). These results demonstrate that PerR is involved in the regulation of iron homeostasis and oxidative stress responses and that it contributes to the virulence of S. pyogenes.
Links	PubMed PMC128242
Keywords	ATP-Binding Cassette Transporters/genetics; Animals; Bacterial Proteins/genetics; Bacterial Proteins/metabolism; Base Sequence; DNA, Bacterial/genetics; Female; Genome, Bacterial; Homeostasis; Hydrogen Peroxide/pharmacology; Iron/metabolism; Mice; Mice, Inbred BALB C; Oxidative Stress; Repressor Proteins/genetics; Repressor Proteins/metabolism; Streptococcus pyogenes/genetics; Streptococcus pyogenes/growth & development; Streptococcus pyogenes/metabolism; Streptococcus pyogenes/pathogenicity; Transcription Factors; Virulence/genetics; Virulence/physiology
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
STRP1:Q491D8		GO:0000303: response to superoxide	IMP: Inferred from Mutant Phenotype:	P	Figure 4.	complete CACAO 8346
STRP1:Q491D8		GO:0009405: pathogenesis	IMP: Inferred from Mutant Phenotype:	P	Figure 5.	complete CACAO 8347
STRP1:Q491D8		GO:0042542: response to hydrogen peroxide	IMP: Inferred from Mutant Phenotype:	P	Figure 3.	complete CACAO 8348
STRP1:Q491D8		GO:0055072: iron ion homeostasis	IMP: Inferred from Mutant Phenotype:	P	Figure 1.	complete CACAO 8349

References

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