How can systems approaches help us understand and treat infectious disease?
How can systems approaches help us understand and treat infectious disease?
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系统方法如何帮助我们理解和治疗传染病？
DOI：
10.1016/j.cels.2022.11.009
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发表时间：
2022
期刊：
影响因子：
9.3
通讯作者：
Germain,RonaldN
中科院分区：
文献类型：
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作者：
Kuchina,Anna;Yang,Jason;Aldridge,Bree;Janes,KevinA;Subramanian,Naeha;Krogan,NevanJ;Bouhaddou,Mehdi;Einav,Shirit;Papin,Jason;Germain,RonaldN
传染病是一个广义的术语，描述了宿主生物体与许多种类的病原体的相互作用。然而，对所有这些人来说，日益严重的问题是抗生素耐药性（AMR）的出现和快速传播，导致了持续的全球健康危机。这个问题非常复杂，非常适合用系统方法来解决，包括收集、整合和分析宿主和进化病原体的大规模、高分辨率、纵向数据集。有多种方法可以使这些方法在设计更好的治疗方法方面非常有用，这将阻止病原体进化遗传抗性或呈现暂时的耐药状态（如药物持久性）的机会。特别是，针对宿主和病原菌的高通量、大规模、单细胞分辨率组学技术的出现，现在为询问难以捉摸的、罕见的表型持续状态奠定了基础，表型持续状态暂时允许一部分细胞在没有遗传变化的情况下耐受治疗，导致停止治疗后感染复发。确定导致致病菌亚群在不同条件下形成持久性的基因调控网络变化将为联合疗法提供新的靶点，这些疗法将利用所发现的漏洞并阻止表型向持久性转变。此外，需要系统方法来理解结构化细菌群落或生物膜的基本设计原理，这是许多持续性感染病例的基础，并有助于使它们易于治疗。
Unraveling persistence Infectious disease is a broad term that describes the interactions of a host organism with many classes of pathogens. However, the rising issue for all of them is the emergence and rapid spread of antimicrobial resistance (AMR) contributing to an ongoing global health crisis. This problem is very complex and well-suited to be tackled with systems approaches, which include collecting, integrating, and analyzing large-scale, high-resolution, longitudinal datasets for both the host and the evolving pathogen. There are multiple ways in which such approaches could be tremendously useful to design better treatments, which would block the opportunity for the pathogen to either evolve genetic resistance or assume a temporary drug-tolerant state such as drug persistence. In particular, the advent of high-throughput, massive-scale, single-cell resolution omics technologies for both the host and the pathogenic bacteria now sets the stage for the interrogation of the elusive, rare state of phenotypic persistence, which temporarily permits a fraction of cells to tolerate the treatment in the absence of genetic change, causing the relapse of infection after ceasing the therapy. Identifying the gene regulatory network changes that lead to a subpopulation of pathogenic bacteria developing persistence under different conditions will provide new targets for combination therapies that would exploit the discovered vulnerabilities and block the phenotypic transition to persistence. In addition, systems approaches are needed to understand the fundamental design principles of structured bacterial communities, or biofilms, which underlie many cases of persistent infections, and to help render them susceptible to treatment.