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dc.contributor.authorMancilla, Marcos-
dc.contributor.authorGrilló, María Jesús-
dc.contributor.authorMiguel, María Jesús de-
dc.contributor.authorLópez-Goñi, Ignacio-
dc.contributor.authorSan Román, Beatriz-
dc.contributor.authorZabalza-Baranguá, Ana-
dc.contributor.authorMoriyón, Ignacio-
dc.identifierdoi: 10.1186/1297-9716-44-105-
dc.identifierissn: 0928-4249-
dc.identifiere-issn: 1297-9716-
dc.identifier.citationVeterinary Research 44: 105 (2013)-
dc.description.abstractBrucella 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. © 2013 Mancilla et al.; licensee BioMed Central Ltd.-
dc.description.sponsorshipThis work was funded by MINECO (reference project AGL2011-30453-C04) of Spain, the FIMA foundation and the European Union’s FP7/2007-2013 (grant agreement n° 221948, ICONZ - Integrated control of Neglected Zoonoses) and CSIC JAE-Doc program (FSE).-
dc.description.sponsorshipWe also acknowledge institutional support from the Unit of Information Resources for Research at the “Consejo Superior de Investigaciones Científicas” (CSIC) for the article-processing charges contribution.-
dc.publisherBioMed Central-
dc.relation.isversionofPublisher’s version-
dc.titleDeletion of the GI-2 integrase and the wbkA flanking transposase improves the stability of Brucella melitensis Rev 1 vaccine-
dc.description.versionPeer Reviewed-
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