Attenuation of a pathogenic Mycoplasma strain by modification of the obg gene by using synthetic biology approaches

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cg.authorship.typesCGIAR and advanced research instituteen
cg.contributor.affiliationInstitut National de la Recherche Agronomique, Franceen
cg.contributor.affiliationUniversité de Bordeauxen
cg.contributor.affiliationUniversity of Bernen
cg.contributor.affiliationInternational Livestock Research Instituteen
cg.contributor.affiliationJ. Craig Venter Instituteen
cg.contributor.crpLivestock
cg.contributor.donorEuropean Unionen
cg.contributor.donorInvestissements d’Aveniren
cg.contributor.donorNational Science Foundation, United Statesen
cg.contributor.donorConseil National de Recherche Scientifique, Franceen
cg.creator.identifierElise Schieck: 0000-0003-1756-6337
cg.creator.identifierJoerg Jores: 0000-0003-3790-5746
cg.creator.identifierAnne Liljander: 0000-0002-7543-5493
cg.howPublishedFormally Publisheden
cg.identifier.doihttps://doi.org/10.1128/msphere.00030-19en
cg.isijournalISI Journalen
cg.issn2379-5042en
cg.issue3en
cg.journalmSphereen
cg.reviewStatusPeer Reviewen
cg.subject.ilriANIMAL DISEASESen
cg.subject.ilriRESEARCHen
cg.subject.ilriVACCINESen
cg.volume4en
dc.contributor.authorLartigue, C.en
dc.contributor.authorValverde Timana, Y.en
dc.contributor.authorLabroussaa, F.en
dc.contributor.authorSchieck, Elise G.en
dc.contributor.authorLiljander, Anne M.en
dc.contributor.authorSacchini, Flavioen
dc.contributor.authorPosthaus, H.en
dc.contributor.authorBatailler, B.en
dc.contributor.authorSirand-Pugnet, P.en
dc.contributor.authorVashee, S.en
dc.contributor.authorJores, Joergen
dc.contributor.authorBlanchard, Alainen
dc.date.accessioned2019-12-20T12:03:24Zen
dc.date.available2019-12-20T12:03:24Zen
dc.identifier.urihttps://hdl.handle.net/10568/106289
dc.titleAttenuation of a pathogenic Mycoplasma strain by modification of the obg gene by using synthetic biology approachesen
dcterms.abstractMycoplasma species are responsible for several economically significant livestock diseases for which there is a need for new and improved vaccines. Most of the existing mycoplasma vaccines are attenuated strains that have been empirically obtained by serial passages or by chemical mutagenesis. The recent development of synthetic biology approaches has opened the way for the engineering of live mycoplasma vaccines. Using these tools, the essential GTPase-encoding gene obg was modified directly on the Mycoplasma mycoides subsp. capri genome cloned in yeast, reproducing mutations suspected to induce a temperature-sensitive (TS+) phenotype. After transplantation of modified genomes into a recipient cell, the phenotype of the resulting M. mycoides subsp. capri mutants was characterized. Single-point obg mutations did not result in a strong TS+ phenotype in M. mycoides subsp. capri, but a clone presenting three obg mutations was shown to grow with difficulty at temperatures of ≥40°C. This particular mutant was then tested in a caprine septicemia model of M. mycoides subsp. capri infection. Five out of eight goats infected with the parental strain had to be euthanized, in contrast to one out of eight goats infected with the obg mutant, demonstrating an attenuation of virulence in the mutant. Moreover, the strain isolated from the euthanized animal in the group infected with the obg mutant was shown to carry a reversion in the obg gene associated with the loss of the TS+ phenotype. This study demonstrates the feasibility of building attenuated strains of mycoplasma that could contribute to the design of novel vaccines with improved safety. IMPORTANCE Animal diseases due to mycoplasmas are a major cause of morbidity and mortality associated with economic losses for farmers all over the world. Currently used mycoplasma vaccines exhibit several drawbacks, including low efficacy, short time of protection, adverse reactions, and difficulty in differentiating infected from vaccinated animals. Therefore, there is a need for improved vaccines to control animal mycoplasmoses. Here, we used genome engineering tools derived from synthetic biology approaches to produce targeted mutations in the essential GTPase-encoding obg gene of Mycoplasma mycoides subsp. capri. Some of the resulting mutants exhibited a marked temperature-sensitive phenotype. The virulence of one of the obg mutants was evaluated in a caprine septicemia model and found to be strongly reduced. Although the obg mutant reverted to a virulent phenotype in one infected animal, we believe that these results contribute to a strategy that should help in building new vaccines against animal mycoplasmoses.en
dcterms.accessRightsOpen Access
dcterms.audienceScientistsen
dcterms.bibliographicCitationLartigue, C., Valverde Timana, Y., Labroussaa, F., Schieck, E., Liljander, A., Sacchini, F., Posthaus, H., Batailler, B., Sirand-Pugnet, P., Vashee, S., Jores, J. and Blanchard, A. 2019. Attenuation of a pathogenic Mycoplasma strain by modification of the obg gene by using synthetic biology approaches. mSphere 4(3): e00030-19.en
dcterms.issued2019-06-26
dcterms.languageen
dcterms.licenseCC-BY-4.0
dcterms.publisherAmerican Society for Microbiologyen
dcterms.subjectmycoplasmaen
dcterms.subjectgenomesen
dcterms.subjectvaccinesen
dcterms.subjectresearchen
dcterms.subjectanimal diseasesen
dcterms.subjectpathogenicityen
dcterms.typeJournal Article

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