Caracterización de los sistemas de captación de hierro y zinc del patógeno animal Pasteurella multocida
Iron and zinc are essential for the normal growth of almost all the microorganisms, being the uptake mechanisms of these cations elemental for the infective process of pathogenic bacterial. Moreover, in Gram negative bacterial, the iron receptor proteins are located in the outer membrane, making them good candidates in the vaccine design.
In this framework, the doctoral thesis aim have been to go deeply into the study of divalent cations uptake mechanisms in Pasteurella multocida, a pathogenic bacterial that has an effect on a wide variety of animals, originating important economic losses in the stock sector.
In this study it has been identified a 60-kDa iron receptor, named HbpA, which regulation mechanism is different to that used commonly by the bacterial, because it is Fur pathway independent, being its regulation Fe2+, Mn2+ and haemin dependent. It has being demonstrated that the codifying gene of this protein has a programmed translational frameshift giving rise to a 40 kDa protein. The function of this protein has been characterized as well, demonstrating that it binds both haemin and haemoglobin and this union capacity is maintained in the truncated derivate protein. Furthermore, the antigenicity and its potential protective ability have been studied, showing that HbpA and its truncated derivate are antigenic, but there is non-protective effect when this protein is given in challenge experiments using a mouse animal model.
In reference to the zinc uptake pathways in P. multocida, unknown until the present, it has been characterized the high affinity uptake system (znuABC) genes, showing that there is a distance of 820 kb between znuA and znuCB genes, and znuC and znuB are part of the same transcriptional unit. Contrary to what happens in Escherichia coli and other bacterial, in which the Zur protein controls the expression of this high affinity uptake system; in P. multocida has not been found a homolog to this Zur protein. Nevertheless, it could be established that, in this pathogen, the responsible protein of the znuA and znuCB control is the Fur protein, joined with the Zn2+ and Fe2+ ions.
Finally, using znuA and znuC mutants, it has also been demonstrated that these genes are essential for the virulence in P. multocida.
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Advisor:Barbé García, Jordi; Llagostera Casas, Montserrat
School:Universitat Autónoma de Barcelona
Source Type:Master's Thesis
Keywords:409 departament de genetica i microbiologia
Date of Publication:11/11/2005