The stringent response and Mycobacterium tuberculosis pathogenesis.
The stringent response and Mycobacterium tuberculosis pathogenesis.
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DOI：
10.1093/femspd/fty054
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发表时间：
2018-06
影响因子：
3.3
通讯作者：
J. Prusa;Dennis X. Zhu;Christina L. Stallings
中科院分区：
文献类型：
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作者：
J. Prusa;Dennis X. Zhu;Christina L. Stallings
在感染期间，宿主通过施加一系列压力来抑制结核分枝杆菌（Mtb）的增殖。尽管受到如此猛烈的攻击，但结核分枝杆菌能够在宿主的一生中持续存在，这表明这种病原体具有大量的分子机制来抵抗宿主造成的损害。严格的反应是细菌中保守的全局应激反应，涉及产生高磷酸化的鸟嘌呤核苷酸ppGpp和pppGpp（统称为(p)ppGpp）。(p)ppGpp随后调节许多细胞过程来调节细菌的生理机能，以促进细菌在不同环境中的生存。在宿主产生的压力下存活是成功病原体的基本品质，严格的反应对许多致病菌的细胞内存活至关重要。此外，严格的反应与毒力基因表达、持久性、潜伏期和药物耐受性有关。在结核分枝杆菌中，(p)ppGpp合成是在低营养条件下、长期培养和动物模型慢性感染期间存活所必需的，所有这些都表明在暴露于与感染相关的应激时对(p)ppGpp有严格的要求。在这篇综述中，我们讨论(p)ppGpp代谢及其如何作为结核分枝杆菌毒力的关键调节因子。
During infection, the host restrains Mycobacterium tuberculosis (Mtb) from proliferating by imposing an arsenal of stresses. Despite this onslaught of attacks, Mtb is able to persist for the lifetime of the host, indicating that this pathogen has substantial molecular mechanisms to resist host-inflicted damage. The stringent response is a conserved global stress response in bacteria that involves the production of the hyperphosphorylated guanine nucleotides ppGpp and pppGpp (collectively called (p)ppGpp). (p)ppGpp then regulates a number of cellular processes to adjust the physiology of the bacteria to promote survival in different environments. Survival in the presence of host-generated stresses is an essential quality of successful pathogens, and the stringent response is critical for the intracellular survival of a number of pathogenic bacteria. In addition, the stringent response has been linked to virulence gene expression, persistence, latency and drug tolerance. In Mtb, (p)ppGpp synthesis is required for survival in low nutrient conditions, long term culture and during chronic infection in animal models, all indicative of a strict requirement for (p)ppGpp during exposure to stresses associated with infection. In this review we discuss (p)ppGpp metabolism and how this functions as a critical regulator of Mtb virulence.