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Structural modification of the Pseudomonas aeruginosa alkylquinoline cell–cell communication signal, HHQ, leads to benzofuranoquinolines with anti-virulence behaviour in ESKAPE pathogens

2023-03Journal article Open Access
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dc.contributor.authorROSSETTO, VERONICA
dc.contributor.authorMoore-Machacek, Ay'sha
dc.contributor.authorWoods, David F.
dc.contributor.authorGalvão, Helena M.
dc.contributor.authorShanahan, Rachel M.
dc.contributor.authorHickey, Aobha
dc.contributor.authorO’Leary, Niall
dc.contributor.authorO’Gara, Fergal
dc.contributor.authorMcGlacken, Gerard P.
dc.contributor.authorReen, F. Jerry
dc.date.accessioned2023-04-17T09:55:35Z
dc.date.available2023-04-17T09:55:35Z
dc.date.issued2023-03
dc.description.abstractMicrobial populations have evolved intricate networks of negotiation and communication through which they can coexist in natural and host ecosystems. The nature of these systems can be complex and they are, for the most part, poorly understood at the polymicrobial level. The Pseudomonas Quinolone Signal (PQS) and its precursor 4- hydroxy- 2-heptylquinoline (HHQ) are signal molecules produced by the important nosocomial pathogen Pseudomonas aeruginosa. They are known to modulate the behaviour of co-colonizing bacterial and fungal pathogens such as Bacillus atropheaus, Candida albicans and Aspergillus fumigatus. While the structural basis for alkyl-quinolone signalling within P. aeruginosa has been studied extensively, less is known about how structural derivatives of these molecules can influ-ence multicellular behaviour and population- level decision-making in other co-colonizing organisms. In this study, we investigated a suite of small molecules derived initially from the HHQ framework, for anti-virulence activity against ESKAPE pathogens, at the species and strain levels. Somewhat surprisingly, with appropriate substitution, loss of the alkyl chain (present in HHQ and PQS) did not result in a loss of activity, presenting a more easily accessible synthetic framework for investigation. Virulence profiling uncovered significant levels of inter-strain variation among the responses of clinical and environmental isolates to small-molecule challenge. While several lead compounds were identified in this study, further work is needed to appreciate the extent of strain- level tolerance to small-molecule anti-infectives among pathogenic organisms.pt_PT
dc.description.sponsorshipNational Forum for the Enhancement of Teaching and Learning in Higher Education SFI/12/IP/1315, US Cystic Fibrosis Foundation SFI/12/RC/2275, National Health and Medical Research Council (NHMRC) of Australia SFI/12/RC/2275_P2, UCC Strategic Research Fund and Science Foundation Ireland (SFI) SSPC-3 12/RC/2275_2, Synthesis and Solid State Pharmaceutical Centre (SSPC) HRB-ILP-POR-2019-004, MRCG-2018-16, Universidade do Algarve TL19UCC1481/02, OGARA1710, APP1183640 2020-5,pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.doi10.1099/mic.0.001303pt_PT
dc.identifier.eissn1465-2080
dc.identifier.urihttp://hdl.handle.net/10400.1/19466
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherMicrobiology Societypt_PT
dc.relationCentre for Marine and Environmental Research (CIMA)
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectAntimicrobial resistancept_PT
dc.subjectAnti-virulencept_PT
dc.subjectBiofilmpt_PT
dc.subjectESKAPE pathogenspt_PT
dc.subjectHHQpt_PT
dc.subjectPseudomonas aeruginosapt_PT
dc.titleStructural modification of the Pseudomonas aeruginosa alkylquinoline cell–cell communication signal, HHQ, leads to benzofuranoquinolines with anti-virulence behaviour in ESKAPE pathogenspt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleCentre for Marine and Environmental Research (CIMA)
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F00350%2F2020/PT
oaire.citation.issue3pt_PT
oaire.citation.titleMicrobiologypt_PT
oaire.citation.volume169pt_PT
oaire.fundingStream6817 - DCRRNI ID
person.familyNameROSSETTO
person.familyNameGalvão
person.givenNameVERONICA
person.givenNameHelena
person.identifier1291299
person.identifier.ciencia-idC51A-2C5A-CF8D
person.identifier.orcid0000-0002-4267-0315
person.identifier.orcid0000-0003-0939-8994
person.identifier.scopus-author-id6505974701
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication0840a3e9-660b-47fb-aa52-1b1f751728b1
relation.isAuthorOfPublicationef31f343-34f9-4aec-a095-e070235d23b3
relation.isAuthorOfPublication.latestForDiscovery0840a3e9-660b-47fb-aa52-1b1f751728b1
relation.isProjectOfPublication607b395b-b4ff-4b27-b6e4-779cdea78d97
relation.isProjectOfPublication.latestForDiscovery607b395b-b4ff-4b27-b6e4-779cdea78d97

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