加拿大麦克马斯特大学John C. Whitney与美国麻省理工学院Michael T. Laub等研究人员合作发现，一种菌间毒素通过合成（p）ppApp来抑制靶细胞生长。相关论文于2019年11月6日在线发表在《自然》杂志上。
研究人员在机会性病原体铜绿假单胞菌中鉴定出VI型分泌效应物Tas1。Tas1的晶体结构表明，它与合成（p）ppGpp的酶类似，后者是细菌中一种广泛保存的信号分子，可调节细胞的生长速度，特别是对营养压力的响应。但是，Tas1不能合成（p）ppGpp。相反，它焦磷酸化腺苷核苷酸，以每分钟近18万个分子的速度生成（p）ppApp。
因此，将Tas1传递到竞争细胞中会导致（p）ppApp迅速积累、ATP耗竭以及基本代谢途径的广泛失调，从而导致靶细胞死亡。
这项发现揭示了细菌间拮抗作用的新型机制，并证明了代谢产物（p）ppApp在细菌中的生理作用。
据介绍，细菌已进化出复杂的机制来抑制竞争者的生长。一种这样的机制涉及VI型分泌系统，细菌可利用该系统将抗菌毒素直接注入邻近的细胞。这些毒素中有许多靶向细胞包膜的完整性，但对生长抑制机制的了解尚不全面。
附：英文原文
Title: An interbacterial toxin inhibits target cell growth by synthesizing (p)ppApp
Author: Shehryar Ahmad, Boyuan Wang, Matthew D. Walker, Hiu-Ki R. Tran, Peter J. Stogios, Alexei Savchenko, Robert A. Grant, Andrew G. McArthur, Michael T. Laub, John C. Whitney
Issue&Volume: 2019-11-06
Abstract: Bacteria have evolved sophisticated mechanisms to inhibit the growth of competitors1. One such mechanism involves type VI secretion systems, which bacteria can use to inject antibacterial toxins directly into neighbouring cells. Many of these toxins target the integrity of the cell envelope, but the full range of growth inhibitory mechanisms remains unknown2. Here we identify a type VI secretion effector, Tas1, in the opportunistic pathogen Pseudomonas aeruginosa. The crystal structure of Tas1 shows that it is similar to enzymes that synthesize (p)ppGpp, a broadly conserved signalling molecule in bacteria that modulates cell growth rate, particularly in response to nutritional stress3. However, Tas1 does not synthesize (p)ppGpp; instead, it pyrophosphorylates adenosine nucleotides to produce (p)ppApp at rates of nearly 180,000 molecules per minute. Consequently, the delivery of Tas1 into competitor cells drives rapid accumulation of (p)ppApp, depletion of ATP, and widespread dysregulation of essential metabolic pathways, thereby resulting in target cell death. Our findings reveal a previously undescribed mechanism for interbacterial antagonism and demonstrate a physiological role for the metabolite (p)ppApp in bacteria. The bacterium Pseudomonas aeruginosa attacks competing bacteria using the toxin Tas1, which pyrophosphorylates adenosine nucleotides to generate (p)ppApp, thereby depleting ATP and disrupting multiple cellular functions.
DOI: 10.1038/s41586-019-1735-9
Source:https://www.nature.com/articles/s41586-019-1735-9
Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html
本期文章：《自然》：Online/在线发表
