Liu Yu, Wang Hongyang, Cui Tao, Zhou Xiling, Jia Yanxia, Zhang Hua, He Zheng-Guo
National Key Laboratory of Agricultural Microbiology, Department of Biological Science, College of Life Science and Technology, Huazhong Agricultural University, Wuhan, 430070, China.
Division of Biological Imaging, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
Mol Microbiol. 2016 Jul;101(1):167-81. doi: 10.1111/mmi.13383. Epub 2016 May 7.
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.
类核相关蛋白（NAPs）在细菌染色体的整体组织中发挥着重要作用。然而，分枝杆菌中潜在的NAPs及其功能几乎未被表征。在本研究中，碱性蛋白NapM作为一种新的NAP发挥作用。NapM在所有已测序的分枝杆菌基因组中均保守，并且能够以长度依赖性但序列非依赖性的方式识别DNA。它偏好富含AT的DNA并结合到大沟中。NapM具有明确的DNA桥接功能，并且能够保护DNA免受DNase I消化。NapM全局调控超过150个基因的表达以及耻垢分枝杆菌对两种抗结核药物利福平和乙胺丁醇的抗性。发现一个ABC转运蛋白操纵子专门负责耻垢分枝杆菌对乙胺丁醇的napM依赖性抗性。NapM在结核分枝杆菌中也呈现出类似的抗结核药物抗性调控。这些结果表明NapM是分枝杆菌NAP家族的一个新成员。我们的发现扩展了已鉴定NAPs的范围，并增进了对分枝杆菌中NAPs与抗生素抗性之间关系的理解。
