Dissecting the regulation of bile-induced biofilm formation in Staphylococcus aureus

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dc.contributor.authorUlluwishewa, Dulantha
dc.contributor.authorWang, Liang
dc.contributor.authorPereira, Callen
dc.contributor.authorFlynn, Stephanie
dc.contributor.authorCain, Elizabeth
dc.contributor.authorStick, Stephen
dc.contributor.authorReen, F. Jerry
dc.contributor.authorRamsay, Joshua P.
dc.contributor.authorO'Gara, Fergal
dc.contributor.funderCurtin University, Australiaen
dc.contributor.funderSeventh Framework Programmeen
dc.contributor.funderHorizon 2020en
dc.contributor.funderScience Foundation Irelanden
dc.contributor.funderDepartment of Agriculture, Food and the Marineen
dc.contributor.funderFood Institutional Research Measureen
dc.contributor.funderHealth Research Boarden
dc.contributor.funderIrish Thoracic Societyen
dc.contributor.funderMarine Instituteen
dc.contributor.funderTeagascen
dc.date.accessioned2019-10-25T14:25:49Z
dc.date.available2019-10-25T14:25:49Z
dc.date.issued2016-08-01
dc.date.updated2019-10-25T14:05:52Z
dc.description.abstractAspiration of bile into the cystic fibrosis (CF) lung has emerged as a prognostic factor for reduced microbial lung biodiversity and the establishment of often fatal, chronic pathogen infections. Staphylococcus aureus is one of the earliest pathogens detected in the lungs of children with CF, and once established as a chronic infection, strategies for its eradication become limited. Several lung pathogens are stimulated to produce biofilms in vitro in the presence of bile. In this study, we further investigated the effects of bile on S. aureus biofilm formation. Most clinical S. aureus strains and the laboratory strain RN4220 were stimulated to form biofilms with sub-inhibitory concentrations of bovine bile. Additionally, we observed bile-induced sensitivity to aminoglycosides, which we exploited in a bursa aurealis transposon screen to isolate mutants reduced in aminoglycoside sensitivity and augmented in bile-induced biofilm formation. We identified five mutants that exhibited hypersensitivity to bile with respect to bile-induced biofilm formation, three of which carried transposon insertions within gene clusters involved in wall teichoic acid (WTA) biosynthesis or transport. Strain TM4 carried an insertion between the divergently oriented tagH and tagG genes, which encode the putative WTA membrane translocation apparatus. Ectopic expression of tagG in TM4 restored a wild-type bile-induced biofilm response, suggesting that reduced translocation of WTA in TM4 induced sensitivity to bile and enhanced the bile-induced biofilm formation response. We propose that WTA may be important for protecting S. aureus against exposure to bile and that bile-induced biofilm formation may be an evolved response to protect cells from bile-induced cell lysis.en
dc.description.sponsorshipCurtin University, Australia (Health Science Faculty); Irish Department of Agriculture, Food and the Marine; Food Institutional Research Measure (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); The Marine Institute (Beaufort award C2CRA 2007/082); Teagasc (Walsh Fellowship 2013)en
dc.description.statusPeer revieweden
dc.description.versionAccepted Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationUlluwishewa, D., Wang, L., Pereira, C., Flynn, S., Cain, E., Stick, S., Reen, F. J., Ramsay, J. P. and O’Gara, F. (2016) 'Dissecting the regulation of bile-induced biofilm formation in Staphylococcus aureus', Microbiology, 162(8), pp. 1398-1406. doi: 10.1099/mic.0.000317en
dc.identifier.doi10.1099/mic.0.000317en
dc.identifier.endpage1406en
dc.identifier.issn1465-2080
dc.identifier.issued8en
dc.identifier.journaltitleMicrobiologyen
dc.identifier.startpage1398en
dc.identifier.urihttps://hdl.handle.net/10468/8865
dc.identifier.volume162en
dc.language.isoenen
dc.publisherMicrobiology Societyen
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.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.urihttps://www.microbiologyresearch.org/content/journal/micro/10.1099/mic.0.000317
dc.rights© The Authors 2016. The definitive peer reviewed, edited version of this article is published in Microbiology, 162, 8, 2016, https://doi.org/10.1099/mic.0.000317en
dc.subjectAminoglycosidesen
dc.subjectAnti-bacterial agentsen
dc.subjectATP-binding cassette transportersen
dc.subjectBileen
dc.subjectBiofilmsen
dc.subjectCell wallen
dc.subjectCystic fibrosisen
dc.subjectDNA transposable elementsen
dc.subjectHumansen
dc.subjectLungen
dc.subjectMicrobial sensitivity testsen
dc.subjectProtein transporten
dc.subjectStaphylococcal infectionsen
dc.subjectStaphylococcus aureusen
dc.subjectTeichoic Acidsen
dc.subjectCystic fibrosisen
dc.subjectStaphylococcusen
dc.subjectGastro-esophageal refluxen
dc.titleDissecting the regulation of bile-induced biofilm formation in Staphylococcus aureusen
dc.typeArticle (peer-reviewed)en
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