NapM, a new nucleoid-associated protein, broadly regulates gene expression and affects mycobacterial resistance to anti-tuberculosis drugs

NapM, a new nucleoid-associated protein, broadly regulates gene expression and affects mycobacterial resistance to anti-tuberculosis drugs
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NapM 是一种新的类核相关蛋白,广泛调节基因表达并影响分枝杆菌对抗结核药物的耐药性

DOI:
10.1111/mmi.13383
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发表时间:
2016-07-01
影响因子:
3.6
通讯作者:
He, Zheng-Guo
He, Zheng-Guo
中科院分区:
生物学2区
文献类型:
--
作者:
Liu, Yu;Wang, Hongyang;He, Zheng-Guo

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核相关蛋白在细菌染色体的整体组织中起着重要作用。然而,潜在的NAP及其功能在分枝杆菌中几乎没有特征。在这项研究中,NapM,一种碱性蛋白,作为一种新的NAP。NapM在所有已测序的分枝杆菌基因组中是保守的,并且可以以长度依赖但不依赖于序列的方式识别DNA。它喜欢富含AT的DNA,并与大沟结合。NapM具有明显的DNA桥连作用,能保护DNA免受DNase I的消化。NapM在全球范围内调节了150多个基因的表达,以及耻垢分枝杆菌对两种抗结核药物(即利福平和乙胺丁醇)的耐药性。发现ABC转运操纵子特异性地负责M的napM依赖性乙胺丁醇抗性。恶臭NapM对结核分枝杆菌的耐药性也有类似的调节作用。结核这些结果表明,NapM是分枝杆菌NAP家族的新成员。我们的研究结果扩大了确定的NAP的范围,并提高了对NAP与分枝杆菌抗生素耐药性之间关系的理解。
Nucleoid-associated proteins (NAPs) play important roles in the global organization of bacterial chromosomes. However, potential NAPs and their functions are barely characterized in mycobacteria. In this study, NapM, an alkaline protein, functions as a new NAP. NapM is conserved in all of the sequenced mycobacterial genomes, and can recognize DNA in a length-dependent but sequence-independent manner. It prefers AT-rich DNA and binds to the major groove. NapM possesses a clear DNA-bridging function, and can protect DNA from DNase I digestion. NapM globally regulates the expression of more than 150 genes and the resistance of Mycobacterium smegmatis to two anti-tuberculosis drugs, namely, rifampicin and ethambutol. An ABC transporter operon was found to be specifically responsible for the napM-dependent ethambutol resistance of M. smegmatis. NapM also presents a similar regulation of anti-tuberculosis drug resistance in M. tuberculosis. These results suggest that NapM is a new member of the mycobacterial NAP family. Our findings expand the range of identified NAPs and improve the understanding on the relationship between NAPs with antibiotic resistance in mycobacteria.