Full metadata record
DC Field | Value | Language |
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dc.creator | Mancilla, M. (Marcos) | - |
dc.creator | Grillo, M.J. (María Jesús) | - |
dc.creator | Miguel, M.J. (María Jesús) de | - |
dc.creator | Lopez-Goñi, I. (Ignacio) | - |
dc.creator | San-Roman, B. (Beatriz) | - |
dc.creator | Zabalza-Barangua, A. (Ana) | - |
dc.creator | Moriyon, I. (Ignacio) | - |
dc.date.accessioned | 2014-03-25T11:41:57Z | - |
dc.date.available | 2014-03-25T11:41:57Z | - |
dc.date.issued | 2013 | - |
dc.identifier.citation | Mancilla M, Grillo MJ, de Miguel MJ, Lopez-Goni I, San-Roman B, Zabalza-Barangua A, et al. Deletion of the GI-2 integrase and the wbkA flanking transposase improves the stability of Brucella melitensis Rev 1 vaccine. Vet Res 2013 Oct 31;44:105-9716-44-105. | es_ES |
dc.identifier.issn | 0928-4249 | - |
dc.identifier.uri | https://hdl.handle.net/10171/35589 | - |
dc.description.abstract | Brucella melitensis Rev 1 is the best vaccine available for the prophylaxis of small ruminant brucellosis and, indirectly, for reducing human brucellosis. However, Rev 1 shows anomalously high rates of spontaneous dissociation from smooth (S) to rough (R) bacteria, the latter being inefficacious as vaccines. This S-R instability results from the loss of the O-polysaccharide. To overcome this problem, we investigated whether some recently described mechanisms promoting mutations in O-polysaccharide genes were involved in Rev 1 S-R dissociation. We found that a proportion of Rev 1 R mutants result from genome rearrangements affecting the wbo O-polysaccharide loci of genomic island GI-2 and the wbkA O-polysaccharide glycosyltransferase gene of the wbk region. Accordingly, we mutated the GI-2 int gene and the wbk IS transposase involved in those arrangements, and found that these Rev 1 mutants maintained the S phenotype and showed lower dissociation levels. Combining these two mutations resulted in a strain (Rev 2) displaying a 95% decrease in dissociation with respect to parental Rev 1 under conditions promoting dissociation. Rev 2 did not differ from Rev 1 in the characteristics used in Rev 1 typing (growth rate, colonial size, reactivity with O-polysaccharide antibodies, phage, dye and antibiotic susceptibility). Moreover, Rev 2 and Rev 1 showed similar attenuation and afforded similar protection in the mouse model of brucellosis vaccines. We conclude that mutations targeting genes and DNA sequences involved in spontaneous O-polysaccharide loss enhance the stability of a critical vaccine phenotype and complement the empirical stabilization precautions taken during S Brucella vaccine production. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | BioMed Central | es_ES |
dc.relation | info:eu-repo/grantAgreement/EC/FP7/221948 | - |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.subject | O-polysaccharide synthesis | es_ES |
dc.subject | Gram-negative bacteria | es_ES |
dc.subject | Smooth lipopolysaccharide | es_ES |
dc.subject | DNA polymorphism | es_ES |
dc.subject | Genomic island | es_ES |
dc.subject | PCR assay | es_ES |
dc.subject | Abortus | es_ES |
dc.subject | Virulence | es_ES |
dc.subject | Gene | es_ES |
dc.subject | Identification | es_ES |
dc.title | Deletion of the GI-2 integrase and the wbkA flanking transposase improves the stability of Brucella melitensis Rev 1 vaccine | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.identifier.doi | http://dx.doi.org/10.1186/1297-9716-44-105 | es_ES |
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