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The regulator LdhR and the d-lactate dehydrogenase LdhA of Burkholderia multivorans play a role in carbon overflow and in planktonic cellular aggregates formation

2017-07Journal article Open access
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dc.contributor.authorSilva, Inês N.
dc.contributor.authorRamires, Marcelo J.
dc.contributor.authorAzevedo, Lisa A.
dc.contributor.authorGuerreiro, Ana R.
dc.contributor.authorTavares, Andreia C.
dc.contributor.authorBecker, Jörg D.
dc.contributor.authorMoreira, Leonilde M.
dc.date.accessioned2017-07-24T15:38:50Z
dc.date.available2018-08-01T00:30:08Z
dc.date.issued2017-07
dc.descriptionThis paper version is the accepted manuscript posted online 21 July 2017. It has peer-review. This publication hasn't any creative commons license associated. The deposited article version contains attached the supplementary materials within the pdf.pt_PT
dc.description.abstractLysR-type transcriptional regulators (LTTR) are the most commonly found regulators in Burkholderia cepacia complex, comprising opportunistic pathogens causing chronic respiratory infections in cystic fibrosis (CF) patients. Despite LTTRs being global regulators of pathogenicity in several bacteria, few have been characterized in Burkholderia Here, we showed that gene ldhR of B. multivorans encoding a LTTR is co-transcribed with ldhA encoding a d-lactate dehydrogenase, and evaluate their implication in virulence traits like exopolysaccharide (EPS) synthesis and biofilm formation. Comparison of wild-type (WT) and its isogenic ΔldhR mutant grown in medium with 2% d-glucose revealed a negative impact on EPS biosynthesis and on cells' viability in the presence of LdhR. Loss of viability in WT cells was caused by intracellular acidification as consequence of cumulative organic acids secretion including d-lactate, this last one absent from the ΔldhR mutant supernatant. Furthermore, LdhR is implicated in the formation of planktonic cellular aggregates. WT cell aggregates reached 1000 μm after 24 hours in liquid cultures; in contrast to ΔldhR mutant aggregates that never grew more than 60 μm. Overexpression of d-lactate dehydrogenase LdhA in the ΔldhR mutant partially restored formed aggregates size, suggesting a role for fermentation inside aggregates. Similar results were obtained for surface-attached biofilms, with WT cells producing more biofilm. A systematic evaluation of planktonic aggregates in Burkholderia CF clinical isolates showed aggregates in 40 out of 74. As CF patients' lung environment is microaerophilic and bacteria are found as free aggregates/biofilms, LdhR and LdhA might have central roles in adaptation to this environment.IMPORTANCE Cystic fibrosis patients often suffer from chronic respiratory infections caused by several microorganisms. Among them are the Burkholderia cepacia complex bacteria which cause progressive deterioration of lung function and, in some patients, might develop into fatal necrotizing pneumoniae with bacteremia, known as "cepacia syndrome". Burkholderia pathogenesis is multifactorial since they express several virulence factors, form biofilms, and are highly resistant to antimicrobial compounds, making their eradication from the CF patients' airways very difficult. As Burkholderia is commonly found in the CF lungs in the form of cell aggregates and biofilms, the need to investigate the mechanisms of cellular aggregation is obvious. In this study we demonstrate the importance of a d-lactate dehydrogenase and a regulator, in regulating carbon overflow, cellular aggregates and surface-attached biofilm formation. This not only enhances our understanding of Burkholderia pathogenesis, but can also lead to the development of drugs against these proteins to circumvent biofilm formation.pt_PT
dc.description.sponsorshipInstituto Gulbenkian de Ciência (Gene Expression Unit); Programa Operacional 833 Regional de Lisboa 2020 grant: (LISBOA-01-0145-FEDER-007317); Fundação para a Ciência e a Tecnologia grants: (PTDC/QUI-BIQ/118260/2010, UID/BIO/04565/2013, SFRH/BPD/86475/2012).pt_PT
dc.description.versioninfo:eu-repo/semantics/acceptedVersionpt_PT
dc.identifier.citationThe regulator LdhR and the d-lactate dehydrogenase LdhA of Burkholderia multivorans play a role in carbon overflow and in planktonic cellular aggregates formation Inês N. Silva, Marcelo J. Ramires, Lisa A. Azevedo, Ana R. Guerreiro, Andreia C. Tavares, Jörg D. Becker, and Leonilde M. Moreira Appl. Environ. Microbiol. AEM.01343-17; Accepted manuscript posted online 21 July 2017, doi:10.1128/AEM.01343-17pt_PT
dc.identifier.doi10.1128/AEM.01343-17pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.7/777
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherAmerican Society for Microbiologypt_PT
dc.relationLISBOA-01-0145-FEDER-007317pt_PT
dc.relationKINASE- Phosphoproteomics in Burkholderia to assess the role of tyrosine phosphorylation in virulence determinants expression
dc.relationELUCIDATING THE MOLECULAR MECHANISM TRIGGERING MUCOID MORPHOTYPE VARIATION OF BURKHOLDERIA CEPACIA COMPLEX BACTERIA DURING LONG TERM COLONIZATION OF CYSTIC FIBROSIS PATIENT´S AIRWAYS
dc.relation.publisherversionhttp://aem.asm.org/content/early/2017/07/18/AEM.01343-17pt_PT
dc.subjectLysR-family transcriptional regulatorpt_PT
dc.subjectD-lactate dehydrogenasept_PT
dc.subjectBurkholderia multivoranspt_PT
dc.subjectPlanktonic cellular aggregatespt_PT
dc.subjectBiofilmspt_PT
dc.subjectExopolysaccharidept_PT
dc.subjectCystic fibrosispt_PT
dc.titleThe regulator LdhR and the d-lactate dehydrogenase LdhA of Burkholderia multivorans play a role in carbon overflow and in planktonic cellular aggregates formationpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleKINASE- Phosphoproteomics in Burkholderia to assess the role of tyrosine phosphorylation in virulence determinants expression
oaire.awardTitleELUCIDATING THE MOLECULAR MECHANISM TRIGGERING MUCOID MORPHOTYPE VARIATION OF BURKHOLDERIA CEPACIA COMPLEX BACTERIA DURING LONG TERM COLONIZATION OF CYSTIC FIBROSIS PATIENT´S AIRWAYS
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FQUI-BIQ%2F118260%2F2010/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/5876/UID%2FBIO%2F04565%2F2013/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBPD%2F86475%2F2012/PT
oaire.citation.endPage57pt_PT
oaire.citation.issueEpub ahead of printpt_PT
oaire.citation.startPage1pt_PT
oaire.citation.titleApplied and Environmental Microbiologypt_PT
oaire.citation.volumeEpub ahead of printpt_PT
oaire.fundingStream3599-PPCDT
oaire.fundingStream5876
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.embargofctThe deposited article has 13 months of embargo period in terms of access, because of the journal's policies and the publisher's copyright policy. Since the paper has not been published yet, the library service put in this upload an embargo period superior than 6 months, as a securing measure.pt_PT
rcaap.rightsembargoedAccesspt_PT
rcaap.typearticlept_PT
relation.isProjectOfPublication53e30784-d919-4008-9d4d-14ce5ac1d024
relation.isProjectOfPublicationa9f658f7-c7bc-42eb-b8f5-0dc7990b750d
relation.isProjectOfPublication3ecbc951-ae16-4e45-a1f8-9eef6a3754cf
relation.isProjectOfPublication.latestForDiscovery3ecbc951-ae16-4e45-a1f8-9eef6a3754cf

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