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dc.contributor.authorSlinger, Betty L.
dc.contributor.authorDeay, Jacqueline J.
dc.contributor.authorChandler, Josephine R.
dc.contributor.authorBlackwell, Helen E.
dc.identifier.citationSlinger, B.L., Deay, J.J., Chandler, J.R. et al. Potent modulation of the CepR quorum sensing receptor and virulence in a Burkholderia cepacia complex member using non-native lactone ligands. Sci Rep 9, 13449 (2019).
dc.descriptionThis work is licensed under a Creative Commons Attribution 4.0 International License.en_US
dc.description.abstractThe Burkholderia cepacia complex (Bcc) is a family of closely related bacterial pathogens that are the causative agent of deadly human infections. Virulence in Bcc species has been shown to be controlled by the CepI/CepR quorum sensing (QS) system, which is mediated by an N-acyl L-homoserine lactone (AHL) signal (C8-AHL) and its cognate LuxR-type receptor (CepR). Chemical strategies to block QS in Bcc members would represent an approach to intercept this bacterial communication process and further delineate its role in infection. In the current study, we sought to identify non-native AHLs capable of agonizing or antagonizing CepR, and thereby QS, in a Bcc member. We screened a library of AHL analogs in cell-based reporters for CepR, and identified numerous highly potent CepR agonists and antagonists. These compounds remain active in a Bcc member, B. multivorans, with one agonist 250-fold more potent than the native ligand C8-AHL, and can affect QS-controlled motility. Further, the CepR antagonists prolong C. elegans survival in an infection model. These AHL analogs are the first reported non-native molecules that both directly modulate CepR and impact QS-controlled phenotypes in a Bcc member, and represent valuable chemical tools to assess the role of QS in Bcc infections.en_US
dc.publisherNature Researchen_US
dc.rights© The Author(s) 2019.en_US
dc.subjectChemical toolsen_US
dc.titlePotent modulation of the CepR quorum sensing receptor and virulence in a Burkholderia cepacia complex member using non-native lactone ligandsen_US
kusw.kuauthorChandler, Josephine
kusw.kudepartmentHiguchi Biosciences Centeren_US
kusw.kudepartmentMolecular Biosciencesen_US
kusw.oaversionScholarly/refereed, publisher versionen_US
kusw.oapolicyThis item meets KU Open Access policy criteria.en_US

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Except where otherwise noted, this item's license is described as: © The Author(s) 2019.