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dc.contributor.authorMorkunas, Ben
dc.contributor.authorGal, Ben
dc.contributor.authorGalloway, Warrenen
dc.contributor.authorHodgkinson, Jamesen
dc.contributor.authorIbbeson, BMen
dc.contributor.authorTan, YSen
dc.contributor.authorWelch, Martinen
dc.contributor.authorSpring, Daviden
dc.date.accessioned2016-10-12T11:44:06Z
dc.date.available2016-10-12T11:44:06Z
dc.date.issued2016-07-11en
dc.identifier.issn1860-5397
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/260732
dc.description.abstractPyocyanin is a small molecule produced by Pseudomonas aeruginosa that plays a crucial role in the pathogenesis of infections by this notorious opportunistic pathogen. The inhibition of pyocyanin production has been identified as an attractive antivirulence strategy for the treatment of P. aeruginosa infections. Herein, we report the discovery of an inhibitor of pyocyanin production in cultures of wild-type P. aeruginosa which is based around a 4-alkylquinolin-2(1H)-one scaffold. To the best of our knowledge, this is the first reported example of pyocyanin inhibition by a compound based around this molecular framework. The compound may therefore be representative of a new structural sub-class of pyocyanin inhibitors, which could potentially be exploited in in a therapeutic context for the development of critically needed new antipseudomonal agents. In this context, the use of wild-type cells in this study is notable, since the data obtained are of direct relevance to native situations. The compound could also be of value in better elucidating the role of pyocyanin in P. aeruginosa infections. Evidence suggests that the active compound reduces the level of pyocyanin production by inhibiting the cell-cell signalling mechanism known as quorum sensing. This could have interesting implications; quorum sensing regulates a range of additional elements associated with the pathogenicity of P. aeruginosa and there is a wide range of other potential applications where the inhibition of quorum sensing is desirable.
dc.description.sponsorshipThe research leading to these results has received funding from the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007-2013)/ERC grant agreement no [279337/DOS]. In addition, the group research was supported by grants from the Engineering and Physical Sciences Research Council, Biotechnology and Biological Sciences Research Council, Medical Research Council and Welcome Trust. Y.S.T. was supported by an A*STAR Graduate Scholarship.
dc.languageengen
dc.language.isoenen
dc.publisherBeilstein-Institut
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectPseudomonas aeruginosaen
dc.subjectantibacterialen
dc.subjectantivirulenceen
dc.subjectpyocyaninen
dc.subjectquorum sensingen
dc.titleDiscovery of an inhibitor of the production of the Pseudomonas aeruginosa virulence factor pyocyanin in wild-type cells.en
dc.typeArticle
prism.endingPage1433
prism.publicationDate2016en
prism.publicationNameBeilstein Journal of Organic Chemistryen
prism.startingPage1428
prism.volume12en
dc.identifier.doi10.17863/CAM.5886
dcterms.dateAccepted2016-06-30en
rioxxterms.versionofrecord10.3762/bjoc.12.137en
rioxxterms.versionVoRen
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/en
rioxxterms.licenseref.startdate2016-07-11en
dc.contributor.orcidWelch, Martin [0000-0003-3646-1733]
dc.contributor.orcidSpring, David [0000-0001-7355-2824]
dc.identifier.eissn1860-5397
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idEuropean Commission (626191)
pubs.funder-project-idEPSRC (EP/K039520/1)
pubs.funder-project-idEuropean Research Council (279337)
cam.orpheus.successThu Jan 30 10:20:23 GMT 2020 - The item has an open VoR version.*
rioxxterms.freetoread.startdate2100-01-01


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International