Linear peptidomimetics as potent antagonists of Staphylococcus aureus agr quorum sensing

Scientific Reports
Georgia KarathanasiHanne Ingmer

Abstract

Staphylococcus aureus is an important pathogen causing infections in humans and animals. Increasing problems with antimicrobial resistance has prompted the development of alternative treatment strategies, including antivirulence approaches targeting virulence regulation such as the agr quorum sensing system. agr is naturally induced by cyclic auto-inducing peptides (AIPs) binding to the AgrC receptor and cyclic peptide inhibitors have been identified competing with AIP binding to AgrC. Here, we disclose that small, linear peptidomimetics can act as specific and potent inhibitors of the S. aureus agr system via intercepting AIP-AgrC signal interaction at low micromolar concentrations. The corresponding linear peptide did not have this ability. This is the first report of a linear peptide-like molecule that interferes with agr activation by competitive binding to AgrC. Prospectively, these peptidomimetics may be valuable starting scaffolds for the development of new inhibitors of staphylococcal quorum sensing and virulence gene expression.

References

Dec 19, 1995·Proceedings of the National Academy of Sciences of the United States of America·G JiR P Novick
Aug 26, 1998·The New England Journal of Medicine·F D Lowy
Feb 17, 1999·Proceedings of the National Academy of Sciences of the United States of America·P MayvilleT W Muir
May 29, 1999·Antimicrobial Agents and Chemotherapy·B GoodsonJ Winter
Dec 23, 1999·Current Opinion in Microbiology·B L Bassler
Dec 26, 2001·The Journal of Biological Chemistry·Gholson J LyonTom W Muir
Mar 2, 2002·The Lancet Infectious Diseases·R E Hancock
Mar 17, 2004·Peptides·Jon-Paul S Powers, Robert E W Hancock
Oct 16, 2004·The Journal of Peptide Research : Official Journal of the American Peptide Society·T S RygeP R Hansen
Nov 29, 2005·The Lancet Infectious Diseases·Heiman F L WertheimJan L Nouwen
Mar 10, 2006·Bioorganic & Medicinal Chemistry·Trine S Ryge, Paul R Hansen
May 9, 2006·Biochimica Et Biophysica Acta·Igor Zelezetsky, Alessandro Tossi
Feb 22, 2008·Proceedings of the National Academy of Sciences of the United States of America·Nathaniel P ChongsiriwatanaAnnelise E Barron
Mar 14, 2008·Journal of the American Chemical Society·Elizabeth A GeorgeTom W Muir
May 28, 2008·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·George Sakoulas, Robert C Moellering
Aug 21, 2008·Annual Review of Genetics·Richard P Novick, Edward Geisinger
Jan 17, 2009·Proceedings of the National Academy of Sciences of the United States of America·Edward GeisingerRichard P Novick
Nov 18, 2009·Antimicrobial Agents and Chemotherapy·Anita NielsenHanne Ingmer
Jun 8, 2011·Future Medicinal Chemistry·Menachem Shoham
Nov 15, 2011·Critical Reviews in Biotechnology·Mukesh PasupuletiMartin Malmsten
Aug 15, 2013·Methods in Molecular Biology·Paul R Hansen, Jens K Munk
Oct 15, 2013·Chemistry & Biology·Rasmus D JahnsenRobert E W Hancock
Dec 23, 2016·Chembiochem : a European Journal of Chemical Biology·Joseph K VasquezHelen E Blackwell
Dec 26, 2016·Methods in Molecular Biology·Evan F HaneyRobert E W Hancock

❮ Previous
Next ❯

Citations

Jun 24, 2018·Expert Opinion on Drug Discovery·Olapeju Bolarinwa, Jianfeng Cai
Apr 25, 2019·International Journal of Molecular Sciences·Viola Camilla ScoffoneSilvia Buroni
Feb 26, 2019·Frontiers in Cellular and Infection Microbiology·Osmel Fleitas MartínezOctavio Luiz Franco
Oct 24, 2019·Scientific Reports·Pethaiah GunasekaranJeong Kyu Bang

❮ Previous
Next ❯

Methods Mentioned

BETA
PCR

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.