National Key Laboratory of Agricultural Microbiology, Center for Proteomics Research, College of Life Science and Technology, Huazhong Agricultural University, Wuhan 430070, China.
Nucleic Acids Res. 2012 Dec;40(22):11292-307. doi: 10.1093/nar/gks923. Epub 2012 Oct 9.
In a bis-(3'-5')-cyclic dimeric guanosine monophosphate (c-di-GMP)/transcription factor binding screen, we identified Mycobacterium smegmatis Ms6479 as the first c-di-GMP-responsive transcriptional factor in mycobacteria. Ms6479 could specifically bind with c-di-GMP and recognize the promoters of 37 lipid transport and metabolism genes. c-di-GMP could enhance the ability of Ms6479 to bind to its target DNA. Furthermore, our results establish Ms6479 as a global activator that positively regulates the expression of diverse target genes. Overexpression of Ms6479 in M. smegmatis significantly reduced the permeability of the cell wall to crystal violet and increased mycobacterial resistance to anti-tuberculosis antibiotics. Interestingly, Ms6479 lacks the previously reported c-di-GMP binding motifs. Our findings introduce Ms6479 (here designated LtmA for lipid transport and metabolism activator) as a new c-di-GMP-responsive regulator.
在一个双-(3'-5')-环二鸟苷酸(c-di-GMP)/转录因子结合筛选中，我们鉴定出分枝杆菌 Ms6479 是分枝杆菌中第一个 c-di-GMP 反应性转录因子。Ms6479 可以特异性地与 c-di-GMP 结合，并识别 37 个脂质运输和代谢基因的启动子。c-di-GMP 可以增强 Ms6479 与靶 DNA 结合的能力。此外，我们的结果确立了 Ms6479 作为一个全局激活子，正向调节多种靶基因的表达。在耻垢分枝杆菌中过表达 Ms6479 显著降低了细胞壁对结晶紫的通透性，并增加了分枝杆菌对抗结核抗生素的耐药性。有趣的是，Ms6479 缺乏先前报道的 c-di-GMP 结合基序。我们的研究结果将 Ms6479（此处命名为脂质运输和代谢激活物 LtmA）作为一种新的 c-di-GMP 反应性调节剂。
