Department of Biochemistry & Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada.
PLoS Pathog. 2021 May 13;17(5):e1009532. doi: 10.1371/journal.ppat.1009532. eCollection 2021 May.
Bacteria inhabit diverse environmental niches and consequently must modulate their metabolism to adapt to stress. The nucleotide second messengers guanosine tetraphosphate (ppGpp) and guanosine pentaphosphate (pppGpp) (collectively referred to as (p)ppGpp) are essential for survival during nutrient starvation. (p)ppGpp is synthesized by the RelA-SpoT homologue (RSH) protein family and coordinates the control of cellular metabolism through its combined effect on over 50 proteins. While the role of (p)ppGpp has largely been associated with nutrient limitation, recent studies have shown that (p)ppGpp and related nucleotides have a previously underappreciated effect on different aspects of bacterial physiology, such as maintaining cellular homeostasis and regulating bacterial interactions with a host, other bacteria, or phages. (p)ppGpp produced by pathogenic bacteria facilitates the evasion of host defenses such as reactive nitrogen intermediates, acidic pH, and the complement system. Additionally, (p)ppGpp and pyrophosphorylated derivatives of canonical adenosine nucleotides called (p)ppApp are emerging as effectors of bacterial toxin proteins. Here, we review the RSH protein family with a focus on its unconventional roles during host infection and bacterial competition.
细菌栖息在多样化的环境小生境中，因此必须调节其代谢以适应应激。核苷酸第二信使鸟苷四磷酸（ppGpp）和鸟苷五磷酸（pppGpp）（统称为（p）ppGpp）对于营养饥饿期间的存活是必不可少的。（p）ppGpp由 RelA-SpoT 同源物（RSH）蛋白家族合成，并通过其对超过 50 种蛋白质的综合作用来协调对细胞代谢的控制。虽然（p）ppGpp 的作用主要与营养限制有关，但最近的研究表明，（p）ppGpp 和相关核苷酸对细菌生理学的不同方面具有以前被低估的影响，例如维持细胞内稳态和调节细菌与宿主、其他细菌或噬菌体的相互作用。致病性细菌产生的（p）ppGpp 有助于逃避宿主防御，如活性氮中间体、酸性 pH 值和补体系统。此外，（p）ppGpp 和称为（p）ppApp 的经典腺苷核苷酸的焦磷酸化衍生物正在成为细菌毒素蛋白的效应物。在这里，我们重点介绍 RSH 蛋白家族在宿主感染和细菌竞争中的非常规作用。
