Removal of a subset of non-essential genes fully attenuates a highly virulent Mycoplasma strain
| العنوان: | Removal of a subset of non-essential genes fully attenuates a highly virulent Mycoplasma strain |
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| المؤلفون: | Yonathan Arfi, Paul Ssajjakambwe, Suchismita Chandran, Elise Schieck, Laurent Falquet, Nacyra Assad-Garcia, Fabien Labroussaa, Carole Lartigue, Anne Liljander, Michael Hubert Stoffel, Valentina Cippà, Joerg Jores, Horst Posthaus, Li Ma, Sanjay Vashee, Pascal Sirand-Pugnet, Alain Blanchard |
| المساهمون: | Universität Bern- University of Bern [Bern], Partenaires INRAE, International Livestock Research Institute [CGIAR, Nairobi] (ILRI), International Livestock Research Institute [CGIAR, Ethiopie] (ILRI), Consultative Group on International Agricultural Research [CGIAR] (CGIAR)-Consultative Group on International Agricultural Research [CGIAR] (CGIAR), J. Craig Venter Institute [La Jolla, USA] (JCVI), College of Veterinary Medicine, Animal Resources and Biosecurity, University of Bern, Biologie du fruit et pathologie (BFP), Université Bordeaux Segalen - Bordeaux 2-Institut National de la Recherche Agronomique (INRA)-Université Sciences et Technologies - Bordeaux 1, Universite de Fribourg |
| المصدر: | Frontiers in Microbiology Frontiers in Microbiology, Frontiers Media, 2019, 10, pp.664. ⟨10.3389/fmicb.2019.00664⟩ Frontiers in Microbiology, Vol 10 (2019) Jores, Jörg; Ma, Li; Ssajjakambwe, Paul; Schieck, Elise; Liljander, Anne; Chandran, Suchismita; Stoffel, Michael H.; Cippà, Valentina; Arfi, Yonathan; Assad-Garcia, Nacyra; Falquet, Laurent; Sirand-Pugnet, Pascal; Blanchard, Alain; Lartigue, Carole; Posthaus, Horst; Labroussaa, Fabien; Vashee, Sanjay (2019). Removal of a Subset of Non-essential Genes Fully Attenuates a Highly Virulent Mycoplasma Strain. Frontiers in Microbiology, 10(664), p. 664. Frontiers 10.3389/fmicb.2019.00664 <http://dx.doi.org/10.3389/fmicb.2019.00664> Frontiers in Microbiology (10), 664. (2019) |
| بيانات النشر: | Cold Spring Harbor Laboratory, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Microbiology (medical), virulence traits, Saccharomyces cerevisiae, Mutant, lcsh:QR1-502, Virulence, Genomics, 610 Medicine & health, Mycoplasma mycoides subsp. capri, medicine.disease_cause, Microbiology, Genome, lcsh:Microbiology, Genome engineering, 03 medical and health sciences, attenuation, genome engineering, in vivo challenge, Biologie animale, medicine, mollicute, pathologie animale, Gene, Original Research, 030304 developmental biology, Animal biology, Genetics, 0303 health sciences, [SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, 630 Agriculture, biology, Strain (chemistry), santé animale, 030306 microbiology, [SDV.BA]Life Sciences [q-bio]/Animal biology, Mycoplasma, biology.organism_classification, Médecine vétérinaire et santé animal, 570 Life sciences, Veterinary medicine and animal Health, bactérie pathogène |
| الوصف: | Mycoplasmas are the smallest free-living organisms and cause a number of economically important diseases affecting humans, animals, insects and plants. Here, we demonstrate that highly virulentMycoplasma mycoidessubspeciescapri(Mmc) can be fully attenuatedviatargeted deletion of non-essential genes encoding, among others, potential virulence traits. Five genomic regions, representing approximately ten percent of the originalMmcgenome, were successively deleted usingSaccharomyces cerevisiaeas an engineering platform. Specifically, a total of 68 genes out of the 432 genes verified to be individually nonessential in the JCVI-Syn3.0 minimal cell, were excised from the genome.In vitrocharacterization showed that this mutant was similar to its parental strain in terms of its doubling time, even though ten percent of the genome content were removed. A novelin vivochallenge model in goats revealed that the wild-type parental strain caused marked necrotizing inflammation at the site of inoculation, septicemia and all animals reaching endpoint criteria within seven days after experimental infection. This is in contrast to the mutant strain, which caused no clinical signs nor pathomorphological lesions. These results highlight, for the first time, the rational design, construction and complete attenuation of aMycoplasmastrain via synthetic genomics tools. Trait addition using the yeast-based genome engineering platform and subsequentin vitroorin vivotrials employing theMycoplasmachassis will allow us to dissect the role of individual candidateMycoplasmavirulence factors and lead the way for the development of an attenuated designer vaccine.IMPORTANCEMembers of theMycoplasma mycoidescluster cause important animal plaques in Africa and Asia, which impact animal welfare, provision of food and the life of thousands of small-scale farmers. We applied synthetic biology tools toMycoplasma mycoidesin order to design and create a fully attenuatedMycoplasmastrain that was subsequently confirmedin vivousing a novel caprine infection model. This is the first time that aMycoplasmamutant developed by applying synthetic biology tools has been testedin vivoto pin point candidate virulence traits. The mutant strain is similar to “apathogenicE. coliK12” strains that boosted the research on host-pathogen interactions for the genusEscherichiaand other bacterial genera. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1664-302X |
| DOI: | 10.1101/508978 |
| DOI: | 10.3389/fmicb.2019.00664⟩ |
| DOI: | 10.3389/fmicb.2019.00664 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7a51f71dc6c49133ba9cbbe3e38d9d7c |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....7a51f71dc6c49133ba9cbbe3e38d9d7c |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1664302X |
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| DOI: | 10.1101/508978 |