Systems biology approaches to understanding mycobacterial survival mechanisms

Helena I.M. Boshoff , Desmond S. Lun
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引用次数: 18

Abstract

The advent of high-throughput platforms for the interrogation of biological systems at the cellular and molecular levels has allowed living cells to be observed and understood at a hitherto unprecedented level of detail and has enabled the construction of comprehensive, predictive in silico models. Here, we review the application of such high-throughput, systems-biological techniques to mycobacteria – specifically to the pernicious human pathogen Mycobacterium tuberculosis (MTb) and its ability to survive in human hosts. We discuss the development and application of transcriptomic, proteomic, regulomic, and metabolomic techniques for MTb as well as the development and application of genome-scale in silico models. Thus far, systems-biological approaches have largely focused on in vitro models of MTb growth; reliably extending these approaches to in vivo conditions relevant to infection is a significant challenge for the future that holds the ultimate promise of novel chemotherapeutic interventions.

Abstract Image

了解分枝杆菌生存机制的系统生物学方法
在细胞和分子水平上对生物系统进行讯问的高通量平台的出现,使得活细胞在迄今为止前所未有的细节水平上被观察和理解,并使构建全面的、可预测的计算机模型成为可能。在这里,我们回顾了这种高通量、系统生物学技术在分枝杆菌上的应用,特别是对有害的人类病原体结核分枝杆菌(MTb)及其在人类宿主中的生存能力。我们讨论了转录组学、蛋白质组学、规则组学和代谢组学技术在结核分枝杆菌中的发展和应用,以及基因组规模在硅模型中的发展和应用。到目前为止,系统生物学方法主要集中在体外MTb生长模型上;将这些方法可靠地扩展到与感染相关的体内条件是未来的重大挑战,这是新型化疗干预的最终希望。
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