Exploiting interkingdom interactions for development of small-molecule inhibitors of Candida albicans biofilm formation

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dc.contributor.authorReen, F. Jerry
dc.contributor.authorPhelan, John P.
dc.contributor.authorGallagher, Lorna
dc.contributor.authorWoods, David F.
dc.contributor.authorShanahan, Rachel M.
dc.contributor.authorCano, Rafael
dc.contributor.authorÓ Muimhneacháin, Eoin
dc.contributor.authorMcGlacken, Gerard P.
dc.contributor.authorO'Gara, Fergal
dc.contributor.funderScience Foundation Irelanden
dc.contributor.funderSeventh Framework Programmeen
dc.contributor.funderHealth Research Boarden
dc.contributor.funderTeagascen
dc.contributor.funderDepartment of Agriculture, Food and the Marineen
dc.contributor.funderFood Institutional Research Measureen
dc.contributor.funderIrish Research Council for Science, Engineering and Technologyen
dc.contributor.funderMarine Instituteen
dc.contributor.funderIrish Research Councilen
dc.contributor.funderUniversity College Corken
dc.date.accessioned2019-10-23T11:12:32Z
dc.date.available2019-10-23T11:12:32Z
dc.date.issued2016-07-25
dc.date.updated2019-10-23T10:52:01Z
dc.description.abstractA rapid decline in the development of new antimicrobial therapeutics has coincided with the emergence of new and more aggressive multidrug-resistant pathogens. Pathogens are protected from antibiotic activity by their ability to enter an aggregative biofilm state. Therefore, disrupting this process in pathogens is a key strategy for the development of next-generation antimicrobials. Here, we present a suite of compounds, based on the Pseudomonas aeruginosa 2-heptyl-4(1H)-quinolone (HHQ) core quinolone interkingdom signal structure, that exhibit noncytotoxic antibiofilm activity toward the fungal pathogen Candida albicans. In addition to providing new insights into what is a clinically important bacterium-fungus interaction, the capacity to modularize the functionality of the quinolone signals is an important advance in harnessing the therapeutic potential of signaling molecules in general. This provides a platform for the development of potent next-generation small-molecule therapeutics targeting clinically relevant fungal pathogens.en
dc.description.sponsorshipHealth Research Board (HRB (Irish Thoracic Society MRCG-2014-6)); (Walsh Fellowship 2013); Teagasc (Walsh Fellowship 2013); Department of Agriculture, Food and the Marine (Food Institutional Research Measure (FIRM/RSF/CoFoRD, FIRM 08/RDC/629, FIRM 1/F009/MabS, and FIRM 13/F/516)); Irish Research Council for Science, Engineering and Technology ((IRCSET) (PD/2011/2414 and GOIPG/2014/647)); Marine Institute ((Foras Na Mara) (Beaufort award C2CRA 2007/082)); University College Cork (UCC Strategic Research Fund)en
dc.description.statusPeer revieweden
dc.description.versionAccepted Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationReen, F. J., Phelan, J. P., Gallagher, L., Woods, D. F., Shanahan, R. M., Cano, R., Ó Muimhneacháin, E., McGlacken, G. P. and O'Gara, F. (2016) ‘Exploiting interkingdom interactions for the development of small molecule inhibitors of Candida albicans biofilm formation’, Antimicrobial Agents and Chemotherapy, 60(10), pp. 5894-5905. doi: 10.1128/AAC.00190-16en
dc.identifier.doi10.1128/AAC.00190-16en
dc.identifier.endpage5905en
dc.identifier.issn0066-4804
dc.identifier.journaltitleAntimicrobial Agents and Chemotherapyen
dc.identifier.startpage5894en
dc.identifier.urihttps://hdl.handle.net/10468/8847
dc.identifier.volume60en
dc.language.isoenen
dc.publisherAmerican Society for Microbiologyen
dc.relation.projectinfo:eu-repo/grantAgreement/SFI/SFI Research Centres/12/RC/2275/IE/Synthesis and Solid State Pharmaceutical Centre (SSPC)/en
dc.relation.projectinfo:eu-repo/grantAgreement/SFI/SFI Technology and Innovation Development Award (TIDA)/13/TIDA/B2625/IE/Small molecule inhibitors of HIF-1: a new class of anti-cancer therapeutics./en
dc.relation.projectinfo:eu-repo/grantAgreement/SFI/SFI Technology and Innovation Development Award (TIDA)/12/TIDA/B2411/IE/Development of small molecule therapeutics for medical intervention: anti-biofilm inhibitors for the medical device sector./en
dc.relation.projectinfo:eu-repo/grantAgreement/SFI/SFI Technology and Innovation Development Award (TIDA)/12/TIDA/B2405/IE/Optimised detection of key biomarkers of Pseudomonas aeruginosa towards a clinical application/en
dc.relation.projectinfo:eu-repo/grantAgreement/SFI/SFI Technology and Innovation Development Award (TIDA)/14/TIDA/2438/IE/Next Generation Antibiotics: anti-biofilm, anti-pathogenic natural bioactives from marine microorganisms./en
dc.relation.projectinfo:eu-repo/grantAgreement/EC/FP7::SP3::PEOPLE/607786/EU/BluePharmTrain/BLUEPHARMTRAINen
dc.relation.projectinfo:eu-repo/grantAgreement/EC/FP7::SP1::KBBE/312184/EU/Increasing Value and Flow in the Marine Biodiscovery Pipeline/PHARMASEAen
dc.relation.projectinfo:eu-repo/grantAgreement/EC/FP7::SP1::KBBE/311975/EU/Marine Microorganisms: Cultivation Methods for Improving their Biotechnological Applications/MACUMBAen
dc.relation.projectinfo:eu-repo/grantAgreement/EC/FP7::SP1::KBBE/287589/EU/Marine Microbial Biodiversity, Bioinformatics and Biotechnology/MICRO B3en
dc.relation.projectinfo:eu-repo/grantAgreement/EC/FP7::SP3::PEOPLE/256596/EU/Dissecting the role of a novel transcriptional regulator in microbial-host interactomes./MEXT REGULATIONen
dc.relation.projectinfo:eu-repo/grantAgreement/EC/H2020::IA/634486/EU/Industrial Applications of Marine Enzymes: Innovative screening and expression platforms to discover and use the functional protein diversity from the sea/INMAREen
dc.relation.urihttps://aac.asm.org/content/60/10/5894
dc.rights© 2016, American Society for Microbiology. All Rights Reserveden
dc.subject4-Quinolonesen
dc.subjectAntifungal agentsen
dc.subjectBiofilmsen
dc.subjectCandida albicansen
dc.subjectCell Lineen
dc.subjectFungal proteinsen
dc.subjectGene expression regulation, fungalen
dc.subjectHumansen
dc.subjectMembrane glycoproteinsen
dc.subjectPseudomonas aeruginosaen
dc.subjectQuinolonesen
dc.subjectSmall molecule librariesen
dc.titleExploiting interkingdom interactions for development of small-molecule inhibitors of Candida albicans biofilm formationen
dc.typeArticle (peer-reviewed)en
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