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

Thomas Bjarnsholt; Maria van Gennip; Tim H Jakobsen; Louise D Christensen; Peter Østrup Jensen; Michael Givskov

doi:10.1038/nprot.2009.205

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

Thomas Bjarnsholt, Maria van Gennip, Tim H Jakobsen, Louise D Christensen, Peter Østrup Jensen, Michael Givskov

Research output: Contribution to journal › Journal article › Research › peer-review

64 Citations (Scopus)

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.

Original language	English
Journal	Nature Protocols (Print Edition)
Volume	5
Issue number	2
Pages (from-to)	282-93
Number of pages	12
ISSN	1754-2189
DOIs	https://doi.org/10.1038/nprot.2009.205
Publication status	Published - 2010

Bibliographical note

Keywords: Animals; Anti-Bacterial Agents; Bacteria; Bacteriological Techniques; Disease Models, Animal; Drug Resistance, Bacterial; Escherichia coli Infections; Gram-Negative Bacteria; Humans; Lung Diseases; Microscopy, Confocal; Microscopy, Electron, Scanning; Models, Animal; Quorum Sensing

Access to Document

10.1038/nprot.2009.205

Cite this

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title = "In vitro screens for quorum sensing inhibitors and in vivo confirmation of their effect",

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.",

author = "Thomas Bjarnsholt and {van Gennip}, Maria and Jakobsen, {Tim H} and Christensen, {Louise D} and Jensen, {Peter {\O}strup} and Michael Givskov",

note = "Keywords: Animals; Anti-Bacterial Agents; Bacteria; Bacteriological Techniques; Disease Models, Animal; Drug Resistance, Bacterial; Escherichia coli Infections; Gram-Negative Bacteria; Humans; Lung Diseases; Microscopy, Confocal; Microscopy, Electron, Scanning; Models, Animal; Quorum Sensing",

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doi = "10.1038/nprot.2009.205",

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AU - Bjarnsholt, Thomas

AU - van Gennip, Maria

AU - Jakobsen, Tim H

AU - Christensen, Louise D

AU - Jensen, Peter Østrup

AU - Givskov, Michael

N1 - Keywords: Animals; Anti-Bacterial Agents; Bacteria; Bacteriological Techniques; Disease Models, Animal; Drug Resistance, Bacterial; Escherichia coli Infections; Gram-Negative Bacteria; Humans; Lung Diseases; Microscopy, Confocal; Microscopy, Electron, Scanning; Models, Animal; Quorum Sensing

PY - 2010

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N2 - 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.

AB - 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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