Macrocyclic Peptides: Novel Antibiotic Treatment against Staphylococcus Aureus

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Macrocyclic Peptides : Novel antibiotic treatment against Staphyloccocus aureus


Princeton Docket # 20-3668


Researchers at Princeton University and University of Tokyo have combined mRNA display technology with lipid-nanodisc based selections to identify high affinity ligands of the integral membrane sensor domain of the histidine kinase, AgrC. In S. aureus, virulence gene expression is under the control of the accessory gene regulator (agr) quorum sensing system.  Within the agr circuit, AgrC, senses the quorum signal and is critical to the regulation of virulence. QQs are molecules that can bind to the integral membrane sensor domain of AgrC and are potent inhibitors of S. aureus virulence in vitro and in vivo.  The QQs are not only potent inhibitors, but by replacing thiolactone with thioether linkages  the macrocycle is less prone to  hydrolysis, a common decomposition pattern in similar inhibitors.


Antibiotic resistant bacterial infections represent a major public health challenge. Each increase in resistance requires improving treatments and the need for novel  pharmaceuticals. Anti-virulence strategies have been proposed where therapeutic agents are administered to interfere with production of virulence factors rather than directly killing the bacterium. This approach is considered advantageous due to its low selection pressure for resistance build-up and minimal perturbation of the host microbiota. The Quorum Quenchers (QQ) are a collection of macrocyclic peptides which are potent inhibitors of Staphylococcus aureus virulence.




  • Pharmaceutical Treatment


  • New anti-virulence strategy




  • Low Selection Pressure for Resistance


  • Large QQ Analog Space


  • Minimal perturbation of the host microbiota



Intellectual Property & Development Status


Patent protection is pending.

Princeton is currently seeking commercial partners for the further development and commercialization of this opportunity.




Chem. Commun., 2020, 56,11223





Laurie Tzodikov

Princeton University Office of Technology Licensing

(609) 258-7256






Patent Information:
For Information, Contact:
Laurie Tzodikov
Licensing Associates
Princeton University
Aishan Zhao
Qian Xie
Tom Muir
Mareike Wiedmann
Hiroaki Suga