Deletion of the GI-2 integrase and the wbkA flanking transposase improves the stability of Brucella melitensis Rev 1 vaccine
| dc.contributor.author | Mancilla, Marcos | |
| dc.contributor.author | Grilló Dolset, María Jesús | |
| dc.contributor.author | Miguel López, María Jesús de | |
| dc.contributor.author | López Goñi, Ignacio | |
| dc.contributor.author | San Román Aberasturi, Beatriz | |
| dc.contributor.author | Zabalza Baranguá, Ana | |
| dc.contributor.author | Moriyón Uría, Ignacio | |
| dc.contributor.department | IdAB. Instituto de Agrobiotecnología / Agrobioteknologiako Institutua | es_ES |
| dc.date.accessioned | 2014-06-20T06:37:11Z | |
| dc.date.available | 2014-06-20T06:37:11Z | |
| dc.date.issued | 2013 | |
| 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. | en |
| dc.description.sponsorship | This 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). | en |
| dc.format.mimetype | application/pdf | en |
| dc.identifier.doi | 10.1186/1297-9716-44-105 | |
| dc.identifier.issn | 1297-9716 (electronic) | |
| dc.identifier.issn | 0928-4249 (print) | |
| dc.identifier.other | 1278 | |
| dc.identifier.uri | https://academica-e.unavarra.es/handle/2454/10926 | |
| dc.language.iso | eng | en |
| dc.publisher | BioMed Central | en |
| dc.relation.ispartof | Veterinary Research, 2013, 44:105 | en |
| dc.relation.projectID | info:eu-repo/grantAgreement/European Commission/FP7/221948/ | |
| dc.relation.projectID | info:eu-repo/grantAgreement/MICINN//AGL2011-30453-C04-03/ES/ | |
| dc.relation.publisherversion | https://dx.doi.org/10.1186/1297-9716-44-105 | |
| dc.rights | © 2013 Mancilla et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. | en |
| dc.rights.accessRights | info:eu-repo/semantics/openAccess | |
| dc.rights.uri | https://creativecommons.org/licenses/by/2.0/ | |
| dc.subject | Gene | en |
| dc.subject | PCR assay | en |
| dc.subject | Gram-negative bacteria | en |
| dc.subject | Genomic island | en |
| dc.subject | Identification | en |
| dc.subject | O-polysaccharide synthesis | en |
| dc.subject | DNA polymorphism | en |
| dc.subject | Abortus | en |
| dc.subject | Smooth lipopolysaccharide | en |
| dc.subject | Virulence | en |
| dc.title | Deletion of the GI-2 integrase and the wbkA flanking transposase improves the stability of Brucella melitensis Rev 1 vaccine | en |
| dc.type | info:eu-repo/semantics/article | |
| dc.type.version | info:eu-repo/semantics/publishedVersion | |
| dspace.entity.type | Publication | |
| relation.isAuthorOfPublication | b22c2d43-7818-468c-b24a-8acde1b7ae80 | |
| relation.isAuthorOfPublication | 618f91fb-38b4-4e6c-b43b-12075328c848 | |
| relation.isAuthorOfPublication.latestForDiscovery | b22c2d43-7818-468c-b24a-8acde1b7ae80 |