San Román Aberasturi, Beatriz

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https://academica-e.unavarra.es/handle/2454/49988

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San Román Aberasturi

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Beatriz

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Producción Agraria

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0000-0003-1195-0100

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7809

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2013 - 20142
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Subject: DNA polymorphism ×

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    PublicationOpen Access
    Mutants in the lipopolysaccharide of Brucella ovis are attenuated and protect against B. ovis infection in mice
    (BioMed Central, 2014) Soler Lloréns, Pedro; Gil Ramírez, Yolanda; Zabalza Baranguá, Ana; Iriarte, Maite; Conde Álvarez, Raquel; Zúñiga Ripa, Amaia; San Román Aberasturi, Beatriz; Zygmunt, Michel; Vizcaíno, Nieves; Cloeckaert, Axel; Grilló Dolset, María Jesús; Moriyón Uría, Ignacio; López Goñi, Ignacio; IdAB. Instituto de Agrobiotecnología / Agrobioteknologiako Institutua
    Brucella spp. are Gram-negative bacteria that behave as facultative intracellular parasites of a variety of mammals. This genus includes smooth (S) and rough (R) species that carry S and R lipopolysaccharides (LPS), respectively. S-LPS is a virulence factor, and mutants affected in the S-LPS O-polysaccharide (R mutants), core oligosaccharide or both show attenuation. However, B. ovis is naturally R and is virulent in sheep. We studied the role of B. ovis LPS in virulence by mutating the orthologues of wadA, wadB and wadC, three genes known to encode LPS core glycosyltransferases in S brucellae. When mapped with antibodies to outer membrane proteins (Omps) and R-LPS, wadB and wadC mutants displayed defects in LPS structure and outer membrane topology but inactivation of wadA had little or no effect. Consistent with these observations, the wadB and wadC but not the wadA mutants were attenuated in mice. When tested as vaccines, the wadB and wadC mutants protected mice against B. ovis challenge. The results demonstrate that the LPS core is a structure essential for survival in vivo not only of S brucellae but also of a naturally R Brucella pathogenic species, and they confirm our previous hypothesis that the Brucella LPS core is a target for vaccine development. Since vaccine B. melitensis Rev 1 is S and thus interferes in serological testing for S brucellae, wadB mutant represents a candidate vaccine to be evaluated against B. ovis infection of sheep suitable for areas free of B. melitensis.
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    PublicationOpen Access
    Deletion of the GI-2 integrase and the wbkA flanking transposase improves the stability of Brucella melitensis Rev 1 vaccine
    (BioMed Central, 2013) Mancilla, Marcos; Grilló Dolset, María Jesús; Miguel López, María Jesús de; López Goñi, Ignacio; San Román Aberasturi, Beatriz; Zabalza Baranguá, Ana; Moriyón Uría, Ignacio; IdAB. Instituto de Agrobiotecnología / Agrobioteknologiako Institutua
    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.