A structure activity-relationship study of the bacterial signal molecule HHQ reveals swarming motility inhibition in Bacillus atrophaeus

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dc.contributor.authorReen, F. Jerry
dc.contributor.authorShanahan, Rachel
dc.contributor.authorCano, Rafael
dc.contributor.authorO'Gara, Fergal
dc.contributor.authorMcGlacken, Gerard P.
dc.contributor.funderEnvironmental Protection Agencyen
dc.contributor.funderHealth Research Boarden
dc.contributor.funderIrish Research Council for Science Engineering and Technologyen
dc.contributor.funderMarine Instituteen
dc.contributor.funderScience Foundation Irelanden
dc.contributor.funderTeagascen
dc.contributor.funderIrish Research Councilen
dc.contributor.funderDepartment of Agriculture, Food and the Marine, Irelanden
dc.contributor.funderEuropean Commissionen
dc.date.accessioned2016-01-11T12:12:59Z
dc.date.available2016-01-11T12:12:59Z
dc.date.issued2015-04-16
dc.description.abstractThe sharp rise in antimicrobial resistance has been matched by a decline in the identification and clinical introduction of new classes of drugs to target microbial infections. Thus new approaches are being sought to counter the pending threat of a post-antibiotic era. In that context, the use of non-growth limiting small molecules, that target virulence behaviour in pathogens, has emerged as a solution with real clinical potential. We have previously shown that two signal molecules (HHQ and PQS) from the nosocomial pathogen Pseudomonas aeruginosa have modulatory activity towards other microorganisms. This current study involves the synthesis and evaluation of analogues of HHQ towards swarming and biofilm virulence behaviour in Bacillus atrophaeus, a soil bacterium and co-inhibitor with P. aeruginosa. Compounds with altered C6-C8 positions on the anthranilate-derived ring of HHQ, display a surprising degree of biological specificity, with certain candidates displaying complete motility inhibition. In contrast, anti-biofilm activity of the parent molecule was completely lost upon alteration at any position indicating a remarkable degree of specificity and delineation of phenotype.en
dc.description.sponsorshipScience Foundation of Ireland (SFI/12/TIDA/B2405, SFI/12/IP/1315, SFI/09/RFP/CHS2353, SSPC2 12/RC/2275, 13-TIDA-B2625, 07/IN.1/B948;12/TIDA/B2411, 12/TIDA/B2405, 09/RFP/BMT 2350, SSPC2 12/RC/2275); Department of Agriculture, Food and the Marine, Ireland (DAFF11/F/009, MabS, FIRM/RSF/CoFoRD, FIRM 08/RDC/629), Environmental Protection Agency (EPA 2008-PhD/S-2); Irish Research Council for Science, Engineering and Technology; (GOIPG/2014/647; PD/2011/2414; RS/2010/2413); European Commission (H20/20 EU-634486, FP7-PEOPLE-2013-ITN, 607786, OCEAN2012, 287589, FP7-KBBE-2012-6, CP-TP 311975, FP7-KBBE-2012-6, CP-TP-312184, Marie Curie 256596); Marine Institute (Beaufort award C2CRA 2007/ 082); Teagasc (Walsh Fellowship 2013)Health Research Board (HRA/2009/146); Irish Thoracic Society (2014 MRCG/HRB scheme (MRCG/2014/6)en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationREEN, F. J., SHANAHAN, R., CANO, R., O'GARA, F. & MCGLACKEN, G. P. 2015. A structure activity-relationship study of the bacterial signal molecule HHQ reveals swarming motility inhibition in Bacillus atrophaeus. Organic & Biomolecular Chemistry, 13, 5537-5541. http://dx.doi.org/10.1039/C5OB00315Fen
dc.identifier.doi10.1039/C5OB00315F
dc.identifier.endpage5541en
dc.identifier.issn1477-0520
dc.identifier.issued19en
dc.identifier.journaltitleOrganic & Biomolecular Chemistryen
dc.identifier.startpage5537en
dc.identifier.urihttps://hdl.handle.net/10468/2173
dc.identifier.volume13en
dc.language.isoenen
dc.publisherThe Royal Society of Chemistryen
dc.rights© 2015, the Authors. This article is licensed under a Creative Commons Attribution 3.0 Unported Licence.en
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/en
dc.subjectBacillus atrophaeusen
dc.subjectQuinolonesen
dc.subjectAnti-microbial agenten
dc.subjectSynthesis and evaluation of analogues of HHQen
dc.titleA structure activity-relationship study of the bacterial signal molecule HHQ reveals swarming motility inhibition in Bacillus atrophaeusen
dc.typeArticle (peer-reviewed)en
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