Medical Microbiology, Centre for Infection, Division of Cellular & Molecular Medicine, St George's University of London, London, SW17 0RE, UK.
Future Med Chem. 2010 Aug;2(8):1371-83. doi: 10.4155/fmc.10.219.
Understanding how growth state influences Mycobacterium tuberculosis responses to antibiotic exposure provides a window into drug action during patient chemotherapy. In this article, we describe the transcriptional programs mediated by isoniazid (INH) during the transition from log-phase to nonreplicating bacilli, from INH-sensitive to INH-tolerant bacilli respectively, using the Wayne model.
INH treatment did not elicit a transcriptional response from nonreplicating bacteria under microarophilic conditions (NRP2), unlike the induction of a robust and well-characterized INH signature in log-phase bacilli.
The differential regulation (between drug-free NRP2 and log-phase bacilli) of genes directly implicated in INH resistance could not account for the abrogation of INH killing in nongrowing bacilli. Thus, factors affecting the requirement for mycolic acids and the redox status of bacilli are likely responsible for the reduction in INH efficacy. We speculate on additional mechanisms revealed by transcriptome analysis that might account for INH tolerance.
了解生长状态如何影响结核分枝杆菌对抗生素暴露的反应，为了解患者化疗期间药物作用提供了一个窗口。在本文中，我们使用 Wayne 模型描述了异烟肼（INH）在从对数期到非复制杆菌的转变过程中，分别从 INH 敏感菌到 INH 耐受菌的转录程序。
在微需氧条件下（NRP2），非复制细菌没有对 INH 产生转录反应，而在对数期细菌中，INH 诱导了一个强大而特征明显的 INH 特征。
直接参与 INH 耐药的基因的差异调控（在无药 NRP2 和对数期细菌之间）不能解释非生长细菌中 INH 杀菌作用的丧失。因此，影响分枝杆菌中类脂酸需求和氧化还原状态的因素可能导致 INH 疗效降低。我们推测转录组分析揭示了可能导致 INH 耐受的其他机制。
