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Attenuation of a Pathogenic Mycoplasma Strain by Modification of the obg Gene by Using Synthetic Biology Approaches.

hal.structure.identifierBiologie du fruit et pathologie [BFP]
dc.contributor.authorLARTIGUE, Carole
hal.structure.identifierBiologie du fruit et pathologie [BFP]
dc.contributor.authorVALVERDE TIMANA, Véronica
hal.structure.identifierBiologie du fruit et pathologie [BFP]
hal.structure.identifierUniversität Bern / University of Bern [UNIBE]
dc.contributor.authorLABROUSSAA, Fabien
hal.structure.identifierInternational Livestock Research Institute [CGIAR, Nairobi] [ILRI]
dc.contributor.authorSCHIECK, Elise
hal.structure.identifierInternational Livestock Research Institute [CGIAR, Nairobi] [ILRI]
dc.contributor.authorLILJANDER, Anne
hal.structure.identifierInternational Livestock Research Institute [CGIAR, Nairobi] [ILRI]
dc.contributor.authorSACCHINI, Flavio
hal.structure.identifierInstitute of Veterinary Pathology
dc.contributor.authorPOSTHAUS, Horst
hal.structure.identifierBiologie du fruit et pathologie [BFP]
dc.contributor.authorBATAILLER, Brigitte
hal.structure.identifierBiologie du fruit et pathologie [BFP]
dc.contributor.authorSIRAND-PUGNET, Pascal
hal.structure.identifierJ. Craig Venter Institute [La Jolla, USA] [JCVI]
dc.contributor.authorVASHEE, Sanjay
hal.structure.identifierUniversität Bern / University of Bern [UNIBE]
hal.structure.identifierInternational Livestock Research Institute [CGIAR, Nairobi] [ILRI]
dc.contributor.authorJORES, Joerg
hal.structure.identifierBiologie du fruit et pathologie [BFP]
dc.contributor.authorBLANCHARD, Alain
dc.date.issued2019
dc.description.abstractEnMycoplasma 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.
dc.language.isoen
dc.publisherAmerican Society for Microbiology.
dc.rights.urihttp://creativecommons.org/licenses/by/
dc.subjectSaccharomyces cerevisiae
dc.subjectgenome transplantation
dc.subjectvaccines
dc.subject.enGTPase Obg
dc.subject.enMycoplasma
dc.subject.enattenuated strain
dc.subject.engenome engineering
dc.subject.entemperature sensitivity
dc.title.enAttenuation of a Pathogenic Mycoplasma Strain by Modification of the obg Gene by Using Synthetic Biology Approaches.
dc.typeArticle de revue
dc.identifier.doi10.1128/mSphere.00030-19
dc.subject.halSciences du Vivant [q-bio]/Biologie animale/Médecine vétérinaire et santé animal
bordeaux.journalMSphere
bordeaux.pagee00030-19
bordeaux.volume4
bordeaux.issue3
bordeaux.peerReviewedoui
hal.identifierhal-02619676
hal.version1
hal.popularnon
hal.audienceInternationale
hal.origin.linkhttps://hal.archives-ouvertes.fr//hal-02619676v1
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=MSphere&rft.date=2019&rft.volume=4&rft.issue=3&rft.spage=e00030-19&rft.epage=e00030-19&rft.au=LARTIGUE,%20Carole&VALVERDE%20TIMANA,%20V%C3%A9ronica&LABROUSSAA,%20Fabien&SCHIECK,%20Elise&LILJANDER,%20Anne&rft.genre=article


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