Sandbox Reserved 772: Difference between revisions

Line 51:

This bifunctional enzyme converts L-histidinol to L-histidine through a L-histidinaldehyde intermediate. <ref name="pnas">http://www.pnas.org.prox.lib.ncsu.edu/content/99/4/1859.full.pdf</ref>

==Implications or Possible Applications==

Brucellosis,

1

most commonly known as Malta fever or undulant

fever, is the most widespread bacterial zoonosis worldwide. Its

causative agent, Brucella spp. , is a facultative intracellular

pathogen developing inside the host’s macrophages, and patho-genesis is linked to this intramacrophagic replication. Due to its

intracellular localization, eradication of Brucella spp. with stan-dard chemotherapy strategies such as antibiotic treatment is

delicate.

2

Moreover, clinical isolates show that drug-resistant

Brucella strains are developing. The absence of a vaccine for

humans

3

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 suishas shown that among others,

genes involved in the biosynthesis of amino acids are essential for

the virulence of the bacteria.

4

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 multipli-cation 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>

==References==

Sandbox Reserved 772: Difference between revisions

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@@ Line 51: / Line 51: @@
 This bifunctional enzyme converts L-histidinol to L-histidine through a L-histidinaldehyde intermediate. <ref name="pnas">http://www.pnas.org.prox.lib.ncsu.edu/content/99/4/1859.full.pdf</ref>
+==Implications or Possible Applications==
+Brucellosis,
+most commonly known as Malta fever or undulant
+fever, is the most widespread bacterial zoonosis worldwide. Its
+causative agent, Brucella spp. , is a facultative intracellular
+pathogen developing inside the host’s macrophages, and patho-genesis is linked to this intramacrophagic replication. Due to its
+intracellular localization, eradication of Brucella spp. with stan-dard chemotherapy strategies such as antibiotic treatment is
+delicate.
+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 suishas 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).
+–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 multipli-cation 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>
 ==References==
 <references />