Hamde Feyissa, Dinka Hunduma, Naimuddin Mohammed
Department of Applied Biology, School of Applied Natural Science, Adama Science and Technology University, P.O. Box 1888, Adama, Ethiopia.
J Genet Eng Biotechnol. 2022 Mar 31;20(1):53. doi: 10.1186/s43141-022-00331-6.
Mycobacterium colombiense is an acid-fast, non-motile, rod-shaped mycobacterium confirmed to cause respiratory disease and disseminated infection in immune-compromised patients, and lymphadenopathy in immune-competent children. It has virulence mechanisms that allow them to adapt, survive, replicate, and produce diseases in the host. To tackle the diseases caused by M. colombiense, understanding of the regulation mechanisms of its genes is important. This paper, therefore, analyzes transcription start sites, promoter regions, motifs, transcription factors, and CpG islands in TetR family transcriptional regulatory (TFTR) genes of M. colombiense CECT 3035 using neural network promoter prediction, MEME, TOMTOM algorithms, and evolutionary analysis with the help of MEGA-X.
The analysis of 22 protein coding TFTR genes of M. colombiense CECT 3035 showed that 86.36% and 13.64% of the gene sequences had one and two TSSs, respectively. Using MEME, we identified five motifs (MTF1, MTF2, MTF3, MTF4, and MTF5) and MTF1 was revealed as the common promoter motif for 100% TFTR genes of M. colombiense CECT 3035 which may serve as binding site for transcription factors that shared a minimum homology of 95.45%. MTF1 was compared to the registered prokaryotic motifs and found to match with 15 of them. MTF1 serves as the binding site mainly for AraC, LexA, and Bacterial histone-like protein families. Other protein families such as MATP, RR, σ-70 factor, TetR, LytTR, LuxR, and NAP also appear to be the binding candidates for MTF1. These families are known to have functions in virulence mechanisms, metabolism, quorum sensing, cell division, and antibiotic resistance. Furthermore, it was found that TFTR genes of M. colombiense CECT 3035 have many CpG islands with several fragments in their CpG islands. Molecular evolutionary genetic analysis showed close relationship among the genes.
We believe these findings will provide a better understanding of the regulation of TFTR genes in M. colombiense CECT 3035 involved in vital processes such as cell division, pathogenesis, and drug resistance and are likely to provide insights for drug development important to tackle the diseases caused by this mycobacterium. We believe this is the first report of in silico analyses of the transcriptional regulation of M. colombiense TFTR genes.
哥伦比亚分枝杆菌是一种抗酸、无运动性、杆状的分枝杆菌，已证实可导致免疫功能低下患者发生呼吸道疾病和播散性感染，以及免疫功能正常儿童发生淋巴结病。它具有使它们能够在宿主体内适应、存活、复制并引发疾病的毒力机制。为了应对由哥伦比亚分枝杆菌引起的疾病，了解其基因的调控机制很重要。因此，本文利用神经网络启动子预测、MEME、TOMTOM算法以及借助MEGA-X进行的进化分析，对哥伦比亚分枝杆菌CECT 3035的TetR家族转录调节（TFTR）基因中的转录起始位点、启动子区域、基序、转录因子和CpG岛进行了分析。
对哥伦比亚分枝杆菌CECT 3035的22个蛋白质编码TFTR基因的分析表明，分别有86.36%和13.64%的基因序列具有一个和两个转录起始位点。使用MEME，我们鉴定出五个基序（MTF1、MTF2、MTF3、MTF4和MTF5），并且MTF1被揭示为哥伦比亚分枝杆菌CECT 3035的100% TFTR基因的共同启动子基序，它可能作为具有至少95.45%同源性的转录因子的结合位点。将MTF1与已注册的原核基序进行比较，发现它与其中15个匹配。MTF1主要作为AraC、LexA和细菌类组蛋白家族的结合位点。其他蛋白质家族，如MATP、RR、σ-70因子、TetR、LytTR、LuxR和NAP似乎也是MTF1的结合候选者。已知这些家族在毒力机制、代谢、群体感应、细胞分裂和抗生素抗性中具有功能。此外，发现哥伦比亚分枝杆菌CECT 3035的TFTR基因有许多CpG岛，其CpG岛中有几个片段。分子进化遗传分析表明这些基因之间关系密切。
我们相信这些发现将有助于更好地理解哥伦比亚分枝杆菌CECT 3035中参与细胞分裂、发病机制和耐药性等重要过程的TFTR基因的调控，并且可能为开发针对这种分枝杆菌引起的疾病的重要药物提供见解。我们相信这是关于哥伦比亚分枝杆菌TFTR基因转录调控的计算机分析的首次报告。
