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dc.contributor.authorRuotsalainen, Pilvi
dc.contributor.authorPenttinen, Reetta
dc.contributor.authorMattila, Sari
dc.contributor.authorJalasvuori, Matti
dc.date.accessioned2019-11-13T07:07:26Z
dc.date.available2019-11-13T07:07:26Z
dc.date.issued2019
dc.identifier.citationRuotsalainen, P., Penttinen, R., Mattila, S., & Jalasvuori, M. (2019). Midbiotics : conjugative plasmids for genetic engineering of natural gut flora. <i>Gut Microbes</i>, <i>10</i>(6), 643-653. <a href="https://doi.org/10.1080/19490976.2019.1591136" target="_blank">https://doi.org/10.1080/19490976.2019.1591136</a>
dc.identifier.otherCONVID_29714031
dc.identifier.otherTUTKAID_81145
dc.identifier.urihttps://jyx.jyu.fi/handle/123456789/66340
dc.description.abstractThe possibility to modify gut bacterial flora has become an important goal, and various approaches are used to achieve desirable communities. However, the genetic engineering of existing microbes in the gut, which are already compatible with the rest of the community and host immune system, has not received much attention. Here, we discuss and experimentally evaluate the possibility to use modified and mobilizable CRISPR-Cas9-endocing plasmid as a tool to induce changes in bacterial communities. This plasmid system (briefly midbiotic) is delivered from bacterial vector into target bacteria via conjugation. Compared to, for example, bacteriophage-based applications, the benefits of conjugative plasmids include their independence of any particular receptor(s) on host bacteria and their relative immunity to bacterial defense mechanisms (such as restriction-modification systems) due to the synthesis of the complementary strand with host-specific epigenetic modifications. We show that conjugative plasmid in association with a mobilizable antibiotic resistance gene targeting CRISPR-plasmid efficiently causes ESBL-positive transconjugants to lose their resistance, and multiple gene types can be targeted simultaneously by introducing several CRISPR RNA encoding segments into the transferred plasmids. In the rare cases where the midbiotic plasmids failed to resensitize bacteria to antibiotics, the CRISPR spacer(s) and their adjacent repeats or larger regions were found to be lost. Results also revealed potential caveats in the design of conjugative engineering systems as well as workarounds to minimize these risks.en
dc.format.mimetypeapplication/pdf
dc.languageeng
dc.language.isoeng
dc.publisherTaylor & Francis
dc.relation.ispartofseriesGut Microbes
dc.rightsCC BY-NC-ND 4.0
dc.subject.othergenetic engineering
dc.subject.otherESBL carriage
dc.subject.otherconjugative plasmid
dc.subject.otherCRISPR editing
dc.subject.otherenterobacteria
dc.titleMidbiotics : conjugative plasmids for genetic engineering of natural gut flora
dc.typearticle
dc.identifier.urnURN:NBN:fi:jyu-201911124852
dc.contributor.laitosBio- ja ympäristötieteiden laitosfi
dc.contributor.laitosDepartment of Biological and Environmental Scienceen
dc.contributor.oppiaineSolu- ja molekyylibiologiafi
dc.contributor.oppiaineNanoscience Centerfi
dc.contributor.oppiaineCell and Molecular Biologyen
dc.contributor.oppiaineNanoscience Centeren
dc.type.urihttp://purl.org/eprint/type/JournalArticle
dc.date.updated2019-11-12T16:15:16Z
dc.description.reviewstatuspeerReviewed
dc.format.pagerange643-653
dc.relation.issn1949-0976
dc.relation.numberinseries6
dc.relation.volume10
dc.type.versionpublishedVersion
dc.rights.copyright© 2019 The Authors
dc.rights.accesslevelopenAccessfi
dc.relation.grantnumber297049
dc.subject.ysogeenitekniikka
dc.subject.ysoenterobakteerit
dc.subject.ysoplasmidit
dc.subject.ysoantibioottiresistenssi
dc.subject.ysosuolistomikrobisto
dc.format.contentfulltext
jyx.subject.urihttp://www.yso.fi/onto/yso/p17994
jyx.subject.urihttp://www.yso.fi/onto/yso/p28554
jyx.subject.urihttp://www.yso.fi/onto/yso/p27720
jyx.subject.urihttp://www.yso.fi/onto/yso/p29640
jyx.subject.urihttp://www.yso.fi/onto/yso/p37925
dc.rights.urlhttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.relation.doi10.1080/19490976.2019.1591136
dc.relation.funderSuomen Akatemiafi
dc.relation.funderAcademy of Finlanden
jyx.fundingprogramAkatemiatutkijan tehtävä, SAfi
jyx.fundingprogramResearch post as Academy Research Fellow, AoFen
jyx.fundinginformationThis work was supported by the Academy of Finland [grant no. 252411 and no. 297049] and Emil Aaltonen Foundation.


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Except where otherwise noted, this item's license is described as CC BY-NC-ND 4.0