title: Zinc metalloenzymes as new targets against the bacterial pathogen Brucella.
abstract: Brucella, a facultative intracellular pathogen, is one of the most common zoonotic diseases worldwide. Considering the alarming health problem caused by the emergence of resistance and multi-resistance of intracellular pathogen, the challenge is currently to identify and to validate novel pharmaceutical targets in this bacteria species. Brucella's genome encodes metalloproteins involved in various biosynthetic processes, some of them being essential during intracellular growth phase and virulence. The potential of prokaryotic zinc metalloproteins such as carbonic anhydrase (CA) and histidinol dehydrogenase (HDH) as anti-Brucella targets has only recently been taken into consideration in the search of novel anti-infective agents that lack of cross-resistance to existing drugs. These enzymes have a growing significance in modern medicine as they are required for growth and/or virulence in several intracellular pathogen species. This review illustrates and describes the progress which has been made in the design and the discovery of selective inhibitors of these bacterial enzymes as new potential anti-Brucella agents.
authors.affiliation: Institut des Biomolécules Max Mousseron (IBMM), UMR 5247 CNRS-Université Montpellier I-Université Montpellier II, 8 rue de l'Ecole Normale, Montpellier Cedex, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Lopez
authors.forename: Stephan
authors.initials: S
authors.lastname: Köhler
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Winum
mesh_terms: D000429:Alcohol Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D041021:Brucella suis / Q000187:drug effects / Q000201:enzymology* / Q000472:pathogenicity; D002256:Carbonic Anhydrases / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D008667:Metalloproteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015394:Molecular Structure; D014774:Virulence / Q000187:drug effects; D015032:Zinc / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; D008667:Metalloproteins; D000429:Alcohol Oxidoreductases; C021358:histidinol dehydrogenase; D002256:Carbonic Anhydrases; D015032:Zinc