Targeting of the Brucella suis virulence factor histidinol dehydrogenase by histidinol analogues results in inhibition of intramacrophagic multiplication of the pathogen.
Brucella suis histidinol dehydrogenase (HDH) can be efficiently targeted by substrate analogues. The growth of this pathogen in minimal medium was inhibited and the multiplication in human macrophages was totally abolished in the presence of the drugs. These effects have been shown to be correlated with the previously described inhibition of Brucella HDH activity.
Joseph
Pascale
P
Centre d'Etudes d'Agents Pathogènes et Biotechnologies pour la Santé (CPBS), CNRS-UM1-UM2, UMR 5236, Université Montpellier II, cc100, Place Eugène Bataillon, 34095, Montpellier Cedex, France. pjoseph@univ-montp2.fr
Abdo
Marie-Rose
MR
Boigegrain
Rose-Anne
RA
Montero
Jean-Louis
JL
Winum
Jean-Yves
JY
Köhler
Stephan
S
D000429:Alcohol Oxidoreductases / Q000037:antagonists & inhibitors*; D041021:Brucella suis / Q000187:drug effects* / Q000254:growth & development / Q000472:pathogenicity; D002006:Brucellosis / Q000382:microbiology; D002460:Cell Line; D003470:Culture Media; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006639:Histidine / Q000494:pharmacology; D006641:Histidinol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006801:Humans; D007659:Ketones / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000382:microbiology*; D013329:Structure-Activity Relationship; D037521:Virulence Factors / Q000037:antagonists & inhibitors*
D003470:Culture Media; D004791:Enzyme Inhibitors; D007659:Ketones; D037521:Virulence Factors; D006639:Histidine; D006641:Histidinol; D000429:Alcohol Oxidoreductases; C021358:histidinol dehydrogenase
Infect Immun. 2001 Jan;69(1):547-50
11119550
J Chem Inf Comput Sci. 2001 Jan-Feb;41(1):196-201
11206374
Vet Microbiol. 2002 Dec 20;90(1-4):299-309
12414150
Proc Natl Acad Sci U S A. 2002 Nov 26;99(24):15711-6
12438693
Trends Microbiol. 2003 May;11(5):215-9
12781524
Proc Natl Acad Sci U S A. 1991 May 15;88(10):4133-7
2034659
Bioorg Med Chem. 2007 Jul 1;15(13):4427-33
17481905
Infect Immun. 1999 Aug;67(8):4041-7
10417172
J Bacteriol. 1950 Jun;59(6):777-82
15436452
Vet Res. 2005 May-Jun;36(3):313-26
15845228
Antimicrob Agents Chemother. 2005 Sep;49(9):3922-5
16127072
Trends Microbiol. 2006 Mar;14(3):109-13
16469497
Cell Mol Life Sci. 2006 Oct;63(19-20):2229-36
16964579
J Leukoc Biol. 1994 Aug;56(2):174-81
8071593