Parsons L M, Waring A L, Limberger R J, Shayegani M
Wadsworth Center, New York State Department of Health, Albany, New York, and School of Public Health, Department of Biomedical Sciences, University at Albany, Albany, NY 12208, USA.
Gene. 1999 Jun 11;233(1-2):109-19. doi: 10.1016/s0378-1119(99)00149-3.
Haemophilus ducreyi, which causes the genital ulcer disease chancroid, requires high basal levels of the 60-kDa heat-shock (hs) protein GroEL in order to survive and adhere to host cells in the presence of common environmental stresses. In contrast, the 70-kDa hs protein, DnaK, a negative modulator of the hs response in prokaryotes, is not produced at as high a level as GroEL. Because of these differences, we were interested in identifying regulatory elements affecting the expression of the H. ducreyi dnaK/dnaJ operon. First, the genes encoding H. ducreyi DnaK (Hsp70) and DnaJ (Hsp40) were sequenced. The deduced amino acid sequences shared 82.8 and 63. 9% identity with the Escherichia coli DnaK and DnaJ homologs, respectively. Despite the presence of highly similar (but not identical) hs promoter sequences preceding both the H. ducreyi groES/groEL and dnaK/dnaJ operons, transcription levels for groEL were found to exceed that of dnaK. Subsequently, other genetic elements that could contribute to a lower basal expression of dnaK in H. ducreyi were identified. These elements include: (1) a complex promoter for dnaK consisting of four transcriptional start points (two for sigma32 and two for sigma70) identified by primer extension; (2) a putative binding site for Fur (a transcriptional repressor of iron-regulated genes) that overlaps the initiating AUG of dnaK; and (3) the potential for extensive secondary structure of the long leader sequences of the dnaK transcripts, which could interfere with efficient translation of DnaK. This unique combination of regulatory elements may be responsible for the relatively low-level expression of dnaK in this fastidious genital pathogen.
引起生殖器溃疡疾病软下疳的杜克雷嗜血杆菌,在常见环境压力存在时,为了存活并黏附于宿主细胞,需要高水平的60 kDa热休克(hs)蛋白GroEL。相比之下,70 kDa的hs蛋白DnaK是原核生物中hs反应的负调节因子,其产生水平不如GroEL高。由于存在这些差异,我们对鉴定影响杜克雷嗜血杆菌dnaK/dnaJ操纵子表达的调控元件感兴趣。首先,对编码杜克雷嗜血杆菌DnaK(Hsp70)和DnaJ(Hsp40)的基因进行了测序。推导的氨基酸序列与大肠杆菌DnaK和DnaJ同源物分别具有82.8%和63.9%的同一性。尽管在杜克雷嗜血杆菌groES/groEL和dnaK/dnaJ操纵子之前都存在高度相似(但不相同)的hs启动子序列,但发现groEL的转录水平超过了dnaK。随后,鉴定出了其他可能导致杜克雷嗜血杆菌中dnaK基础表达较低的遗传元件。这些元件包括:(1)通过引物延伸鉴定出的由四个转录起始点(两个用于sigma32,两个用于sigma70)组成的dnaK复合启动子;(2)一个与dnaK的起始AUG重叠的Fur(铁调节基因的转录抑制因子)假定结合位点;(3)dnaK转录本长前导序列广泛二级结构的可能性,这可能会干扰DnaK的有效翻译。这种独特的调控元件组合可能是这种苛求的生殖器病原体中dnaK相对低水平表达的原因。