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

TY - JOUR

T1 - In vitro screens for quorum sensing inhibitors and in vivo confirmation of their effect

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 - 2010/2

Y1 - 2010/2

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.

U2 - 10.1038/nprot.2009.205

DO - 10.1038/nprot.2009.205

M3 - Journal article

C2 - 20134428

SN - 1754-2189

VL - 5

SP - 282

EP - 293

JO - Nature Protocols

JF - Nature Protocols

IS - 2

ER -