Estudio sobre el papel de los lípidos de ornitina, ácido lactobacílico y fosfatidil-colina en la biología de brucella

Tesis doctoral de Leyre Palacios Chaves

The brucellae are gram negative bacteria that cause an important zoonosis. These bacteria trigger a low proinflammatory response during early infection that allows them to reach intracellular niches before immunity activation. The role of ornithine lipids, phosphatidylcholine and lactobacillic acid in brucella abortus virulence was investigated. We generated mutants in the two genes involved in ornithine lipid synthesis. Ornithine lipid deficiency did not alter the surface properties, promoted proinflammatory responses or generated attenuation. Moreover, in comparison with bordetella pertussis, brucella ornithine lipids lacked a marked pathogen-associated molecular pattern. Concerning phosphatidylcholine, previously described as necessary for brucella virulence, we demonstrated two transporters (chox1 and chox2) the mutation of which abrogated choline uptake but did not generate attenuation, suggesting that brucella is not a choline auxotroph in the host and that either there is endogenous choline synthesis for the phosphatidylcholine synthase pathway or that the phosphatidylethanolamine methylation patway is active. In fact, intermediate precursors of this pathway were identified in b. Melitensis and b. Suis. However, a triple mutant in chox1 and chox2 and the methyltransferase pmta synthesized phosphatidylcholine, suggesting alternative methyltransferases and/or a complex regulation of phosphatidylcholine synthesis. Finally, we identified the brucella cyclopropane fatty acid synthase and demonstrated that its expression was regulated by ph and osmolarity. A synthase mutant was virulent. However, the mutant was sensitive to osmotic stress. It is suggested that, although not necessary in the intracellular life, cyclopropane acyl chains help brucellae to survive outside the host, hence bolstering the possibilities of transmission.

 

Datos académicos de la tesis doctoral «Estudio sobre el papel de los lípidos de ornitina, ácido lactobacílico y fosfatidil-colina en la biología de brucella«

  • Título de la tesis:  Estudio sobre el papel de los lípidos de ornitina, ácido lactobacílico y fosfatidil-colina en la biología de brucella
  • Autor:  Leyre Palacios Chaves
  • Universidad:  Navarra
  • Fecha de lectura de la tesis:  16/12/2010

 

Dirección y tribunal

  • Director de la tesis
    • Ignacio Moriyon Uria
  • Tribunal
    • Presidente del tribunal: María Jesús Lopez zabalza
    • clara María Marín alcala (vocal)
    • virginia Aragón fernández (vocal)
    • Luis román Fernández lago (vocal)

 

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