dc.contributor.author	Reen, F. Jerry
dc.contributor.author	Phelan, John P.
dc.contributor.author	Woods, David F.
dc.contributor.author	Shanahan, Rachel
dc.contributor.author	Cano, Rafael
dc.contributor.author	Clarke, Sarah L.
dc.contributor.author	McGlacken, Gerard P.
dc.contributor.author	O'Gara, Fergal
dc.contributor.funder	European Commission	en
dc.contributor.funder	Seventh Framework Programme	en
dc.contributor.funder	Science Foundation Ireland	en
dc.contributor.funder	Marine Institute	en
dc.contributor.funder	Irish Research Council for Science, Engineering and Technology	en
dc.contributor.funder	Health Research Board	en
dc.contributor.funder	Teagasc	en
dc.date.accessioned	2017-01-09T14:59:01Z
dc.date.available	2017-01-09T14:59:01Z
dc.date.issued	2016-12-22
dc.date.updated	2017-01-09T14:35:14Z
dc.description.abstract	Faced with the continued emergence of antibiotic resistance to all known classes of antibiotics, a paradigm shift in approaches toward antifungal therapeutics is required. Well characterized in a broad spectrum of bacterial and fungal pathogens, biofilms are a key factor in limiting the effectiveness of conventional antibiotics. Therefore, therapeutics such as small molecules that prevent or disrupt biofilm formation would render pathogens susceptible to clearance by existing drugs. This is the first report describing the effect of the Pseudomonas aeruginosa alkylhydroxyquinolone interkingdom signal molecules 2-heptyl-3-hydroxy-4-quinolone and 2-heptyl-4-quinolone on biofilm formation in the important fungal pathogen Aspergillus fumigatus. Decoration of the anthranilate ring on the quinolone framework resulted in significant changes in the capacity of these chemical messages to suppress biofilm formation. Addition of methoxy or methyl groups at the C5–C7 positions led to retention of anti-biofilm activity, in some cases dependent on the alkyl chain length at position C2. In contrast, halogenation at either the C3 or C6 positions led to loss of activity, with one notable exception. Microscopic staining provided key insights into the structural impact of the parent and modified molecules, identifying lead compounds for further development.	en
dc.description.sponsorship	European Commission (FP7-PEOPLE-2013-ITN, 607786; FP7-KBBE-2012-6, CP-TP-312184; FP7-KBBE-2012-6, 311975; OCEAN 2011-2, 287589; Marie Curie 256596; EU-634486); Science Foundation Ireland ( SFI SSPC-2, 12/RC/2275; 13/TIDA/B2625; 12/TIDA/B2411; 12/TIDA/B2405; 14/TIDA/2438, grant number SFI/12/RC/2275); Marine Institute (Beaufort award C2CRA 2007/082); Department of Agriculture and Food, Ireland (FIRM/RSF/CoFoRD; FIRM 08/RDC/629; FIRM 1/F009/MabS; FIRM 13/F/516); Irish Research Council for Science, Engineering and Technology (PD/2011/2414; GOIPG/2014/647); Health Research Board/Irish Thoracic Society (MRCG-2014-6); Teagasc (Walsh Fellowship 2013)	en
dc.description.status	Peer reviewed	en
dc.description.version	Published Version	en
dc.format.mimetype	application/pdf	en
dc.identifier.citation	Reen, F. J., Phelan, J. P., Woods, D. F., Shanahan, R., Cano, R., Clarke, S., McGlacken, G. P. and O’Gara, F. (2016) 'Harnessing Bacterial Signals for Suppression of Biofilm Formation in the Nosocomial Fungal Pathogen Aspergillus fumigatus', Frontiers in Microbiology, 7(2074). doi:10.3389/fmicb.2016.02074	en
dc.identifier.doi	10.3389/fmicb.2016.02074
dc.identifier.endpage	2074-12	en
dc.identifier.issn	1664-302X
dc.identifier.journaltitle	Frontiers In Microbiology	en
dc.identifier.startpage	2074-1	en
dc.identifier.uri	https://hdl.handle.net/10468/3451
dc.identifier.volume	7	en
dc.language.iso	en	en
dc.publisher	Frontiers Media	en
dc.relation.project	info:eu-repo/grantAgreement/EC/FP7::SP3::PEOPLE/607786/EU/BluePharmTrain/BLUEPHARMTRAIN	en
dc.relation.project	info:eu-repo/grantAgreement/EC/FP7::SP1::KBBE/312184/EU/Increasing Value and Flow in the Marine Biodiscovery Pipeline/PHARMASEA	en
dc.relation.project	info:eu-repo/grantAgreement/EC/FP7::SP1::KBBE/287589/EU/Marine Microbial Biodiversity, Bioinformatics and Biotechnology/MICRO B3	en
dc.relation.project	info:eu-repo/grantAgreement/EC/FP7::SP3::PEOPLE/256596/EU/Dissecting the role of a novel transcriptional regulator in microbial-host interactomes./MEXT REGULATION	en
dc.relation.project	info: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/INMARE	en
dc.rights	© 2016 Reen, Phelan, Woods, Shanahan, Cano, Clarke, McGlacken and O’Gara. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.	en
dc.rights.uri	https://creativecommons.org/licenses/by/4.0/	en
dc.subject	Biofilm	en
dc.subject	Aspergillus fumigatus	en
dc.subject	Pseudomonas aeruginosa	en
dc.subject	Interkingdom Interactions	en
dc.subject	Alkylhydroxyquinolone (AHQ)	en
dc.subject	PQS	en
dc.subject	HHQ	en
dc.title	Harnessing bacterial signals for suppression of biofilm formation in the nosocomial fungal pathogen Aspergillus fumigatus	en
dc.type	Article (peer-reviewed)	en

Harnessing bacterial signals for suppression of biofilm formation in the nosocomial fungal pathogen Aspergillus fumigatus

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