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A Staphylococcus aureus regulatory system that responds to host heme and modulates virulence - PMC

Official websites use. Share sensitive information only on official, secure websites. Corresponding Author : Eric P. Skaar 21 st Avenue South, MCN A, Nashville, TN, Tel: Fax: eric. Identifying the molecular machinery that is activated upon infection is central to understanding staphylococcal pathogenesis.

We describe here the H eme- S ensor S ystem HssRS that responds to heme exposure and activates expression of the H eme R egulated T ransporter HrtAB. The coordinated activities of HssRS and HrtAB maintain intracellular heme homeostasis and modulate S.

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Inactivation of the Hss or Hrt systems leads to increased virulence in a vertebrate infection model, a phenotype that is associated with an inhibited innate immune response. Genomic analyses have identified orthologous Hss and Hrt systems in Bacillus anthracis , Listeria monocytogenes, and Enterococcus faecalis , suggesting a conserved regulatory system by which Gram positive pathogens sense heme as a molecular marker of internal host tissue and modulate virulence.

Staphylococcus aureus is one of the most significant infectious threats to global public health Fridkin et al. Infections with S. In order for S. Once inside the host, S. Although virulence gene regulation is one of the most well studied aspects of staphylococcal pathogenesis Bronner et al. The expression of these effectors in vivo is presumably coordinated by a network of two-component systems TCS and transcriptional regulators.

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Although the contributions of a subset of TCS agr , saeRS , srrAB , arlSR and lytRS to virulence gene expression have been studied extensively Bronner et al. In this regard, environmental cues such as high salt, cell density, glucose, energy availability, pH, and subinhibitory antibiotics have been found to affect S.

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