Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2013 May 29;135(21):7869-82.
doi: 10.1021/ja3112115. Epub 2013 May 17.

Highly potent inhibitors of quorum sensing in Staphylococcus aureus revealed through a systematic synthetic study of the group-III autoinducing peptide

Yftah Tal-Gan  1 , Danielle M Stacy, Mary K Foegen, David W Koenig, Helen E Blackwell
Affiliations

Highly potent inhibitors of quorum sensing in Staphylococcus aureus revealed through a systematic synthetic study of the group-III autoinducing peptide

Yftah Tal-Gan et al. J Am Chem Soc. .

Abstract

Methods to intercept bacterial quorum sensing (QS) have attracted significant attention as potential anti-infective therapies. Staphylococcus aureus is a major human pathogen that utilizes autoinducing peptide (AIP) signals to mediate QS and thereby regulate virulence. S. aureus strains are categorized into four groups (I-IV) according to their AIP signal and cognate extracellular receptor, AgrC. Each group is associated with a certain disease profile, and S. aureus group-III strains are responsible for toxic shock syndrome and have been underestimated in other infections to date. A limited set of non-native AIP analogs have been shown to inhibit AgrC receptors; such compounds represent promising tools to study QS pathways in S. aureus . We seek to expand this set of chemical probes and report herein the first design, synthesis, and biological testing of AIP-III mimetics. A set of non-native peptides was identified that can inhibit all four of the AgrC receptors (I-IV) with picomolar IC50 values in reporter strains. These analogs also blocked hemolysis by wild-type S. aureus group I-IV strains-a virulence trait under the control of QS-at picomolar concentrations. Moreover, four of the lead AgrC inhibitors were capable of attenuating the production of toxic shock syndrome toxin-1 (also under the control of QS) by over 80% at nanomolar concentrations in a wild-type S. aureus group-III strain. These peptides represent, to our knowledge, the most potent synthetic inhibitors of QS in S. aureus known, and constitute new and readily accessible chemical tools for the study of the AgrC system and virulence in this deadly pathogen.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

Publication types

MeSH terms

LinkOut - more resources