首页> 外文期刊>BMC Genomics >The Mycobacterium tuberculosis transcriptional landscape under genotoxic stress
【24h】

The Mycobacterium tuberculosis transcriptional landscape under genotoxic stress

机译:基因毒性胁迫下结核分枝杆菌的转录景观

获取原文
获取外文期刊封面目录资料

摘要

Background As an intracellular human pathogen, Mycobacterium tuberculosis (Mtb) is facing multiple stressful stimuli inside the macrophage and the granuloma. Understanding Mtb responses to stress is essential to identify new virulence factors and pathways that play a role in the survival of the tubercle bacillus. The main goal of this study was to map the regulatory networks of differentially expressed (DE) transcripts in Mtb upon various forms of genotoxic stress. We exposed Mtb cells to oxidative (H2O2 or paraquat), nitrosative (DETA/NO), or alkylation (MNNG) stress or mitomycin C, inducing double-strand breaks in the DNA. Total RNA was isolated from treated and untreated cells and subjected to high-throughput deep sequencing. The data generated was analysed to identify DE genes encoding mRNAs, non-coding RNAs (ncRNAs), and the genes potentially targeted by ncRNAs. Results The most significant transcriptomic alteration with more than 700 DE genes was seen under nitrosative stress. In addition to genes that belong to the replication, recombination and repair (3R) group, mainly found under mitomycin C stress, we identified DE genes important for bacterial virulence and survival, such as genes of the type VII secretion system (T7SS) and the proline-glutamic acid/proline-proline-glutamic acid (PE/PPE) family. By predicting the structures of hypothetical proteins (HPs) encoded by DE genes, we found that some of these HPs might be involved in mycobacterial genome maintenance. We also applied a state-of-the-art method to predict potential target genes of the identified ncRNAs and found that some of these could regulate several genes that might be directly involved in the response to genotoxic stress. Conclusions Our study reflects the complexity of the response of Mtb in handling genotoxic stress. In addition to genes involved in genome maintenance, other potential key players, such as the members of the T7SS and PE/PPE gene family, were identified. This plethora of responses is detected not only at the level of DE genes encoding mRNAs but also at the level of ncRNAs and their potential targets.
机译:背景技术作为一种细胞内人类病原体,结核分枝杆菌(Mtb)面对巨噬细胞和肉芽肿内的多种压力刺激。了解Mtb对压力的反应对于确定新的毒力因子和在结核杆菌生存中起作用的途径至关重要。这项研究的主要目的是针对各种形式的遗传毒性胁迫绘制Mtb中差异表达(DE)转录本的调控网络图。我们将Mtb细胞暴露于氧化性(H 2 O 2 或百草枯),亚硝化(DETA / NO)或烷基化(MNNG)胁迫或丝裂霉素C诱导双链破坏DNA。从处理过的和未处理过的细胞中分离出总RNA,并进行高通量深度测序。分析产生的数据以鉴定编码mRNA,非编码RNA(ncRNA)的DE基因,以及可能被ncRNA靶向的基因。结果在亚硝化胁迫下观察到了最显着的转录组改变,共有700个DE基因。除了主要在丝裂霉素C胁迫下发现的属于复制,重组和修复(3R)组的基因外,我们还鉴定了对细菌毒力和存活至关重要的DE基因,例如VII型分泌系统(T7SS)和脯氨酸-谷氨酸/脯氨酸-脯氨酸-谷氨酸(PE / PPE)家族。通过预测DE基因编码的假设蛋白(HPs)的结构,我们发现其中一些HP可能参与了分枝杆菌基因组的维护。我们还应用了最先进的方法来预测已鉴定的ncRNA的潜在靶基因,并发现其中一些可以调节可能直接参与对遗传毒性应激反应的多个基因。结论我们的研究反映了Mtb在处理遗传毒性胁迫中反应的复杂性。除了涉及基因组维护的基因外,还鉴定了其他潜在的关键参与者,例如T7SS和PE / PPE基因家族的成员。不仅在编码mRNA的DE基因水平上,而且在ncRNA及其潜在靶标水平上都检测到了这种过多的响应。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号