Attenuating Staphylococcus aureus virulence gene regulation: A medicinal chemistry perspective

Gordon, Christopher P.; Williams, Paul; Chan, Weng C.

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. © 2013 American Chemical Society.

Citation

Gordon, C. P., Williams, P., & Chan, W. C. (2013). Attenuating Staphylococcus aureus virulence gene regulation: A medicinal chemistry perspective. Journal of Medicinal Chemistry, 56(4), 1389-1404. https://doi.org/10.1021/jm3014635

• Journal Article Type: Review
• Online Publication Date: Jan 22, 2013
• Publication Date: Feb 28, 2013
• Deposit Date: Sep 10, 2020
• Journal: Journal of Medicinal Chemistry
• Print ISSN: 0022-2623
• Electronic ISSN: 1520-4804
• Publisher: American Chemical Society
• Peer Reviewed: Peer Reviewed
• Volume: 56
• Issue: 4
• Pages: 1389-1404
• DOI: https://doi.org/10.1021/jm3014635
• Public URL: https://nottingham-repository.worktribe.com/output/3104793
• Publisher URL: https://pubs.acs.org/doi/10.1021/jm3014635