Institut des Biomolécules Max Mousseron (IBMM), UMR 5247 CNRS-Université Montpellier I-Université Montpellier II, 8 rue de l'Ecole Normale, Montpellier Cedex, France.
J Inorg Biochem. 2012 Jun;111:138-45. doi: 10.1016/j.jinorgbio.2011.10.019. Epub 2011 Dec 1.
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.
布氏杆菌是一种兼性细胞内病原体，是全球最常见的人畜共患病之一。考虑到细胞内病原体耐药性和多药耐药性的出现所带来的严重健康问题，目前的挑战是在该细菌物种中识别和验证新的药物靶点。布氏杆菌基因组编码参与各种生物合成过程的金属蛋白酶，其中一些在细胞内生长阶段和毒力中是必需的。原核锌金属蛋白酶（如碳酸酐酶（CA）和组氨酸醇脱氢酶（HDH））作为抗布氏杆菌靶点的潜力，在寻找缺乏与现有药物交叉耐药性的新型抗感染药物时，最近才被考虑。这些酶在现代医学中具有越来越重要的意义，因为它们是几种细胞内病原体生长和/或毒力所必需的。本文综述了设计和发现这些细菌酶的选择性抑制剂作为新的潜在抗布氏杆菌药物方面所取得的进展。
