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==Implications or Possible Applications==
==Implications or Possible Applications==
Brucellosis, most commonly known as Maltafever, is the most widespread bacterial zoonosis worldwide. Its causative agent, Brucella spp., is a facultative intracellular pathogen developed inside the host’s macrophages.
Brucellosis, commonly known as Maltafever, is the most widespread bacterial zoonosis worldwide. Its causative agent, Brucella spp., is a facultative intracellular pathogen developed inside the host’s macrophages.


Pathogenesis is linked to this intramacrophagic replication. Due to its intracellular localization, eradication of Brucella spp. with standard chemotherapy strategies such as antibiotic treatment is delicate.  
The absence of a vaccine for humans and the appearing resistance of Brucella spp. to anti-biotic chemotherapy points to the necessity to develop new therapeutic strategies to eradicate this reemerging pathogen.


Moreover, clinical isolates show that drug-resistant Brucella strains are developing. The absence of a vaccine for humans and the appearing resistance of Brucella spp. to anti-biotic chemotherapy points to the necessity to develop new therapeutic strategies to eradicate this reemerging pathogen.
The virulome analysis of Brucella suis shows that genes involved in the biosynthesis of amino acids are essential for the virulence of the bacteria. Inhibition of its enzymatic activity with specific inhibitors will prevent intramacrophagic multiplication of Brucella. Histidinol dehydrogenase being essential exclusively for the growth of the bacteria inside the macrophage of the host, and having no counterpart in mammalians, it constitutes a therapeutic target for the development of an anti-infectious treatment against intracellular pathogens.
 
The virulome analysis of Brucella suis has shown that among others, genes involved in the biosynthesis of amino acids are essential for the virulence of the bacteria.
 
This new approach consists in targeting a virulence factor of this pathogen, the histidinol dehydrogenase (HDH, EC. 1.1.23). 5–7
 
This metalloenzyme is involved in the final two steps of the biosynthesis of histidine where it catalyses the NAD dependent oxidation of histidinol to histidine via histidinaldehyde.
 
Inhibition of its enzymatic activity with specific inhibitors will prevent intramacrophagic multiplication of Brucella. HDH being essential exclusively for the growth of the bacteria inside the macrophage of the host, and having no counterpart in mammalians, it constitutes a therapeutic target for the development of an anti-infectious treatment against intracellular pathogens.
  <ref name="article2">http://pubs.rsc.org.prox.lib.ncsu.edu/en/content/articlepdf/2011/md/c1md00146a</ref>
  <ref name="article2">http://pubs.rsc.org.prox.lib.ncsu.edu/en/content/articlepdf/2011/md/c1md00146a</ref>


==References==  
==References==  
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