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Attenuating Staphylococcus aureus virulence gene regulation: a medicinal chemistry perspective.


ABSTRACT: Virulence gene expression in Staphylococcus aureus is tightly regulated by intricate networks of transcriptional regulators and two-component signal transduction systems. There is now an emerging body of evidence to suggest that the blockade of S. aureus virulence gene expression significantly attenuates infection in experimental models. In this Perspective, we will provide insights into medicinal chemistry strategies for the development of chemical reagents that have the capacity to inhibit staphylococcal virulence expression. These reagents can be broadly grouped into four categories: (1) competitive inhibitors of the accessory gene regulator (agr) quorum sensing system, (2) inhibitors of AgrA-DNA interactions, (3) RNAIII transcription inhibitors, and (4) inhibitors of the SarA family of transcriptional regulators. We discuss the potential of specific examples of antivirulence agents for the management and treatment of staphylococcal infections.

SUBMITTER: Gordon CP 

PROVIDER: S-EPMC3585718 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature

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Attenuating Staphylococcus aureus virulence gene regulation: a medicinal chemistry perspective.

Gordon Christopher P CP   Williams Paul P   Chan Weng C WC  

Journal of medicinal chemistry 20130122 4


Virulence gene expression in Staphylococcus aureus is tightly regulated by intricate networks of transcriptional regulators and two-component signal transduction systems. There is now an emerging body of evidence to suggest that the blockade of S. aureus virulence gene expression significantly attenuates infection in experimental models. In this Perspective, we will provide insights into medicinal chemistry strategies for the development of chemical reagents that have the capacity to inhibit sta  ...[more]

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2022-12-17 | GSE220798 | GEO