Exposure to bile leads to the emergence of adaptive signalling variants in the opportunistic pathogen Pseudomonas aeruginosa

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dc.contributor.authorFlynn, Stephanie
dc.contributor.authorReen, F. Jerry
dc.contributor.authorO'Gara, Fergal
dc.contributor.funderEnterprise Irelanden
dc.contributor.funderEuropean Commissionen
dc.contributor.funderScience Foundation Irelanden
dc.contributor.funderIrish Research Council for Science, Engineering and Technologyen
dc.contributor.funderHealth Research Boarden
dc.contributor.funderCystic Fibrosis Foundationen
dc.date.accessioned2019-10-06T21:07:23Z
dc.date.available2019-10-06T21:07:23Z
dc.date.issued2019-08-29
dc.description.abstractThe chronic colonization of the respiratory tract by the opportunistic pathogen Pseudomonas aeruginosa is the primary cause of morbidity and mortality in cystic fibrosis (CF) patients. P. aeruginosa has been shown to undergo extensive genomic adaptation facilitating its persistence within the CF lung allowing it to evade the host immune response and outcompete co-colonizing residents of the lung microbiota. However, whilst several studies have described the various mutations that frequently arise in clinical isolates of P. aeruginosa, the environmental factors governing the emergence of these genetic variants is less well characterized. Gastro-oesophageal reflux has recently emerged as a major co-morbidity in CF and is often associated with the presence of bile acids in the lungs most likely by (micro) aspiration. In order to investigate whether bile may select for genetic variants, P. aeruginosa was experimentally evolved in artificial sputum medium, a synthetic media resembling environmental conditions found within the CF lung. Pigmented derivatives of P. aeruginosa emerged exclusively in the presence of bile. Genome sequencing analysis identified single nucleotide polymorphisms (SNPs) in quorum sensing (lasR) and both the pyocyanin (phzS) and pyomelanin (hmgA) biosynthetic pathways. Phenotypic analysis revealed an altered bile response when compared to the ancestral P. aeruginosa progenitor strain. While the recovered pigmented derivatives retained the bile mediated suppression of swarming motility and enhanced antibiotic tolerance, the biofilm, and redox responses to bile were abolished in the adapted mutants. Though loss of pseudomonas quinolone signal (PQS) production in the pigmented isolates was not linked to the altered biofilm response, the loss of redox repression could be explained by defective alkyl-quinolone (AQ) production in the presence of bile. Collectively, these findings suggest that the adaptive variants of P. aeruginosa that arise following long term bile exposure enables the emergence of ecologically competitive sub-populations. Altered pigmentation and AQ signaling may contribute to an enhancement in fitness facilitating population survival within a bile positive environment.en
dc.description.sponsorshipEnterprise Ireland (CF-2017-0757-P, IP-2015-0390); Irish Research Council for Science, Engineering and Technology (GOIPG/2014/647); Health Research Board/Irish Thoracic Society (MRCG-2018-16, MRCG-2014-6); Cystic Fibrosis Foundation, United States (OG1710).en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.articleid2013en
dc.identifier.citationFlynn, S., Reen, F. J. and O’Gara, F. (2019) 'Exposure to Bile Leads to the Emergence of Adaptive Signaling Variants in the Opportunistic Pathogen Pseudomonas aeruginosa', Frontiers in Microbiology, 10, 2013 (13pp.) DOI: 10.3389/fmicb.2019.02013en
dc.identifier.doi10.3389/fmicb.2019.02013en
dc.identifier.eissn1664-302X
dc.identifier.endpage13en
dc.identifier.journaltitleFrontiers in Microbiologyen
dc.identifier.startpage1en
dc.identifier.urihttps://hdl.handle.net/10468/8706
dc.identifier.volume10en
dc.language.isoenen
dc.publisherFrontiers Mediaen
dc.relation.projectinfo:eu-repo/grantAgreement/NHMRC/NHMRC Project Grants/634486/AU/Health Outcomes of Older Indigenous Australians- a 5 year follow up study of a population at risk/en
dc.relation.projectinfo:eu-repo/grantAgreement/SFI/SFI Technology and Innovation Development Award (TIDA)/15/TIDA/2977/IE/Pre-clinical testing of novel fungal biofilm blockers for the medical device sector./en
dc.relation.projectinfo:eu-repo/grantAgreement/SFI/SFI Research Frontiers Programme (RFP)/09/RFP/BMT2350/IE/An investigation of the molecular interactions between statins and microbial pathogens and their combined impact on the human immune response./en
dc.relation.urihttps://www.frontiersin.org/articles/10.3389/fmicb.2019.02013/full
dc.rights©2019 Flynn, Reen 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) and the copyright owner(s) 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.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectPseudomonas aeruginosaen
dc.subjectEvolutionen
dc.subjectAdaptationen
dc.subjectPigmenteden
dc.subjectChronicen
dc.subjectQuorum Sensing (QS)en
dc.subjectBileen
dc.subjectArtificial sputum mediumen
dc.titleExposure to bile leads to the emergence of adaptive signalling variants in the opportunistic pathogen Pseudomonas aeruginosaen
dc.typeArticle (peer-reviewed)en
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