IMR Press / FBL / Volume 7 / Issue 4 / DOI: 10.2741/cheung

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on as a courtesy and upon agreement with Frontiers in Bioscience.

Global regulation of virulence determinants in Staphylococcus aureus by the SarA protein family
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1 Department of Microbiology and Immunology, Dartmouth Medical School, Hanover, NH 03755, USA
2 Department of Immunology, National Jewish Medical and Research Center and Department of Pharmacology, University of Colorado Medical School, Denver, CO 80286, USA
Academic Editor:Peter Zuber
Front. Biosci. (Landmark Ed) 2002, 7(4), 1825–1842;
Published: 1 August 2002
(This article belongs to the Special Issue Prokaryotic transcriptional regulation: beyond the enteric paradigms)

In S. aureus, the production of virulence determinants such as cell wall adhesins and exotoxins during the growth cycle is controlled by global regulators such as SarA and agr. Genomic scan reveals 16 two-component regulatory systems (e.g. agr and sae) as well as a family of SarA homologs in S. aureus. We call the SarA homologs the SarA protein family. Many of the members in this protein family are either small basic proteins (<153 residues) or two-domain proteins in which a single domain shares sequence similarity to each of the small basic proteins. Recent crystal structures of SarR and SarA reveal dimeric structures for these proteins. Because of its structure and unique mode of DNA binding, SarR, and possibly other SarA family members, may belong to a new functional class of the winged-helix family, accommodating long stretch of DNA with bending points. Based on sequence homology, we hypothesize that the SarA protein family may entail homologous structures with similar DNA-binding motifs but divergent activation domains. An understanding of how these regulators interact with each other in vivo and how they sense environmental signals to control virulence gene expression (e.g. α-hemolysin) will be important to our eventual goal of disrupting the regulatory network.

Staphylococcus Aureus
Global Regulation
Virulence Factors
SarA protein Family
Two-Component Regulation System
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