Zafirlukast inhibits complexation of Lsr2 with DNA and growth of Mycobacterium tuberculosis.
Zafirlukast inhibits complexation of Lsr2 with DNA and growth of Mycobacterium tuberculosis.
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Zafirlukast 抑制 Lsr2 与 DNA 的复合以及结核分枝杆菌的生长。
DOI：
10.1128/aac.02407-12
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发表时间：
2013
影响因子：
4.9
通讯作者：
Ronning,DonaldR
中科院分区：
文献类型：
--
作者：
Pinault,Lucile;Han,Jeong-Sun;Kang,Choong-Min;Franco,Jimmy;Ronning,DonaldR
分枝杆菌类核蛋白Lsr2是一种DNA桥接蛋白，在基因组的缩合和结构组织中发挥作用，并作为基因转录的全局阻遏物。在这里，我们描述的实验表明，扎鲁司特抑制Lsr2和DNA之间的复合在体外。扎鲁司特显示抑制两种不同测试的分枝杆菌的生长，但对大肠杆菌没有显示出生长抑制。通过监测结核分枝杆菌中的转录水平，在体内反映了Lsr2抑制活性。这些数据表明扎鲁司特抑制Lsr2体内功能，促进通常由Lsr2结合的一系列基因表达的失调并阻碍生长。由于扎鲁司特可能通过与当前M.它是结核病药物，目前用作哮喘的预防性治疗，它为开发结核病的新治疗方法提供了一个有趣的线索。
The mycobacterial nucleoid-associated protein Lsr2 is a DNA-bridging protein that plays a role in condensation and structural organization of the genome and acts as a global repressor of gene transcription. Here we describe experiments demonstrating that zafirlukast inhibits the complexation between Lsr2 and DNAin vitro. Zafirlukast is shown to inhibit growth in two different species of mycobacteria tested but exhibits no growth inhibition of Escherichia coli. The Lsr2 inhibitory activity is reflectedin vivoas determined by monitoring of transcription levels in Mycobacterium tuberculosis. These data suggest that zafirlukast inhibits Lsr2 functionin vivo, promoting dysregulation of the expression of an array of genes typically bound by Lsr2 and hindering growth. Since zafirlukast likely operates by a mechanism distinct from current M. tuberculosis drugs and is currently used as a prophylactic treatment for asthma, it offers an intriguing lead for development of new treatments for tuberculosis.