Manchester Interdisciplinary Biocenter, Faculty of Life Sciences, University of Manchester, 131 Princess Street, Manchester M1 7DN, UK.
Future Med Chem. 2010 Aug;2(8):1339-53. doi: 10.4155/fmc.10.216.
The human pathogen Mycobacterium tuberculosis (Mtb) encodes 20 cytochrome P450 (P450) enzymes. Gene essentiality for viability or host infection was demonstrated for Mtb P450s CYP128, CYP121 and CYP125. Structure/function studies on Mtb P450s revealed key roles contributing to bacterial virulence and persistence in the host. Various azole-class drugs bind with high affinity to the Mtb P450 heme and are potent Mtb antibiotics. This paper reviews the current understanding of the biochemistry of Mtb P450s, their interactions with azoles and their potential as novel Mtb drug targets. Mtb multidrug resistance is widespread and novel therapeutics are desperately needed. Simultaneous drug targeting of several Mtb P450s crucial to bacterial viability/persistence could offer a new route to effective antibiotics and minimize the development of drug resistance.
人类病原体结核分枝杆菌（Mtb）编码 20 种细胞色素 P450（P450）酶。已经证明 Mtb P450s CYP128、CYP121 和 CYP125 对生存力或宿主感染具有基因必要性。对 Mtb P450s 的结构/功能研究揭示了对细菌毒力和在宿主中持续存在有贡献的关键作用。各种唑类药物与 Mtb P450 的血红素具有高亲和力，是有效的 Mtb 抗生素。本文综述了 Mtb P450 的生物化学、与唑类药物的相互作用及其作为新型 Mtb 药物靶点的潜力。Mtb 多药耐药性广泛存在，迫切需要新的治疗方法。同时针对对细菌生存/持续至关重要的几种 Mtb P450 进行药物靶向治疗，可能为有效抗生素提供新途径，并最大程度地减少耐药性的发展。
