In vitro screens for quorum sensing inhibitors and in vivo confirmation of their effect.

Nature Protocols
Thomas BjarnsholtMichael Givskov

Abstract

This article will introduce the reader to protocols intended for (i) identification of quorum sensing (QS) inhibitors (QSIs), (ii) characterization of these compounds in vitro and (iii) evaluation of these compounds in animal models. Traditional antimicrobial drugs are designed against planktonic bacteria and not against bacterial biofilms. In biofilms, bacteria are highly resistant to otherwise lethal treatments and they communicate with each other, thus enabling coordinated group behavior. For many years, we have focused on interference with cell to cell communication, also known as QS, with the aim of disabling the expression of virulence and reduction of antibiotic tolerance. Here we present protocols for screening and testing for acyl-homoserine lactone (AHL)-dependent QS inhibition. We also present protocols for the in vivo validation of QSIs as possible drug candidates. The presented methods allow the evaluation of QS inhibition by a potential drug candidate within 2-3 weeks.

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Citations

Apr 8, 2010·Expert Reviews in Molecular Medicine·Thomas BjarnsholtMichael Givskov
May 18, 2011·Antimicrobial Agents and Chemotherapy·Fernando BaqueroFernando de la Cruz
Feb 9, 2012·Antimicrobial Agents and Chemotherapy·Tim Holm JakobsenMichael Givskov
Sep 26, 2013·International Journal of Molecular Sciences·Evelina PapaioannouWim J Quax
Sep 8, 2012·Future Microbiology·Michael Givskov
Jul 12, 2013·Future Microbiology·Tim Holm JakobsenNiels Høiby
Oct 4, 2015·FEMS Microbiology Reviews·Catherine GrandclémentDenis D Faure
Dec 20, 2015·Journal of the American Chemical Society·Jun-Young KimYoung-Tae Chang
Nov 13, 2012·Biotechnology Advances·Vipin Chandra Kalia
Jul 29, 2016·World Journal of Microbiology & Biotechnology·Barış Gökalsın, Nüzhet Cenk Sesal
Dec 16, 2016·Journal of Medicinal Chemistry·July FongMichael Givskov
Apr 15, 2016·Scientific Reports·Jianming ZengCha Chen
Jan 5, 2017·Bioorganic & Medicinal Chemistry·Nripendra N BiswasNaresh Kumar
Dec 4, 2012·ChemMedChem·Søren SkovstrupOlivier Taboureau
Sep 17, 2010·Chemistry : a European Journal·Chambers C Hughes, William Fenical
Oct 2, 2013·Nature Reviews. Drug Discovery·Thomas BjarnsholtNiels Høiby
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Nov 8, 2017·Microbiology·Gwenn G ParungaoRobert M Blumenthal
Aug 6, 2015·World Journal of Clinical Cases·Israel Castillo-JuárezRodolfo García-Contreras
Mar 21, 2020·Pathogens and Disease·Maria AlhedeThomas Bjarnsholt
Apr 4, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Pansong ZhangLin Chen

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