Papel de una etanolamina-fosfato transferasa y una glicosil transferasa en la síntesis del lipopolisacárido de brucella y utilización de una acetil transferasa para la modificación epitópica de la cadena o

Tesis doctoral de Yolanda Teresa Gil Ramírez

Brucellosis is a disease of terrestrial and marine mammals and an important zoonosis. Brucella lipopolysaccharide plays a major role in virulence and is considered as a molecule with a modified pathogen-associated molecular pattern. The role of two hypothetical lipopolysaccharide core glycosyltransferases [bab1_0351 (wadb) and bab1_1620] and a putative phosphoethanolamine transferase (bmei0118) was investigated. a wadb mutant in b. Abortus, b. Melitensis and b. Suis biovar 2 lacked part of the lipopolysaccharide core but kept the o-chain. The wadb b. Abortus mutant was sensitive to normal serum and bactericidal peptides and attenuated in dendritic cells and mice. Moreover, it elicited a protective immunoresponse, confirming that core mutants are promising brucellosis vaccines. On the other hand, bab1_1620, seems not to be related to this process in b. Abortus and its function is not essential for full virulence in mice. it is demonstrated that bmelpta acts as a transferase that incorporate phosphoethanolamine to the lipid a section. This modification contributes to low recognition of lipopolysaccharide by some innate immune effectors since bmelpta mutant was sensitive to normal serum and bactericidal peptides. Bmelpta has orthologous in other alpha-2 proteobacteria such as ochrobactrum, sinorhizobium or agrobacterium. a crucial aspect in the control of brucellosis is that the use of s-brucellae vaccines interferes in the diagnosis, since they generate antibodies against the o-chain of the lipopolysaccharide, which is also the dominant antigen in infected animals. In order to bypass this difficulty, we have followed a new approach. The expression of wbdr (e. Coli o 157:h7 o chain acetyltransferase) in b. Abortus 2308 leads to the incorporation of acetyl residues to the perosamine polysaccharide, creating a new immunogenic epitope that could be the base for the elaboration of new diagnostic tests.

 

Datos académicos de la tesis doctoral «Papel de una etanolamina-fosfato transferasa y una glicosil transferasa en la síntesis del lipopolisacárido de brucella y utilización de una acetil transferasa para la modificación epitópica de la cadena o«

  • Título de la tesis:  Papel de una etanolamina-fosfato transferasa y una glicosil transferasa en la síntesis del lipopolisacárido de brucella y utilización de una acetil transferasa para la modificación epitópica de la cadena o
  • Autor:  Yolanda Teresa Gil Ramírez
  • Universidad:  Navarra
  • Fecha de lectura de la tesis:  13/05/2011

 

Dirección y tribunal

  • Director de la tesis
    • Ignacio Moriyon Uria
  • Tribunal
    • Presidente del tribunal: ignacio Lopez goñi
    • José María Blasco Martinez (vocal)
    • José Antonio Bengoechea alonso (vocal)
    • michel Zygmunt (vocal)

 

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