Tryptophan Availability during Persistence of Chlamydia trachomatis Directly Impacts Expression of Chlamydial Cell Division Proteins.
Tryptophan Availability during Persistence of Chlamydia trachomatis Directly Impacts Expression of Chlamydial Cell Division Proteins.
复制标题
沙眼衣原体持续存在期间色氨酸的可用性直接影响衣原体细胞分裂蛋白的表达。
DOI：
10.1128/iai.00513-22
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发表时间：
2023
影响因子：
3.1
通讯作者：
Ouellette,ScotP
中科院分区：
文献类型：
--
作者：
Riffaud,CamilleM;Rucks,ElizabethA;Ouellette,ScotP
衣原体是一种专性细胞内病原体，其基因组高度减少，缺乏介导严格反应的主要应激反应基因，如relA和spoT。有趣的是，作为一种依赖宿主营养的细胞内细菌和色氨酸（Trp）营养缺陷型，衣原体对色氨酸饥饿非常敏感，色氨酸饥饿是由宿主细胞因子干扰素-γ在体内诱导的。为了应对色氨酸饥饿，衣原体进入一种可生存但不可复制的状态，称为持久性。衣原体持久性的一个主要特征是阻碍细胞分裂。我们假设细胞分裂在持续过程中由于无法翻译富含色氨酸的细胞分裂蛋白而受到阻碍。为了测试这一点，我们首先使用诱导型表达菌株研究了色氨酸饥饿条件下各种细胞分裂蛋白的翻译。我们观察到，色氨酸缺乏蛋白 MurG 和色氨酸中性蛋白 FtsL 在持续期间仍然表达，而富含色氨酸蛋白 Pbp2、RodA、FtsI/Pbp3 和 MraY 的表达显着降低。作为我们假设的概念证明，我们比较了 RodZ 的野生型和突变同工型的表达，其中四个 Trp 密码子发生了突变。这些实验表明，当蛋白质中不存在色氨酸时，RodZ 在持久性期间表达量的下降会逆转，从而将其表达与其色氨酸含量直接联系起来。总之，这些实验表明特定的细胞分裂蛋白在持续期间不会产生。我们的数据首次提供了一种机制，可以解释色氨酸饥饿介导的衣原体持续存在过程中细胞分裂的抑制。
Chlamydia is an obligate intracellular pathogen with a highly reduced genome devoid of major stress response genes likerelAandspoT, which mediate the stringent response. Interestingly, as an intracellular bacterium dependent on its host for nutrients and as a tryptophan (Trp) auxotroph, Chlamydia is very sensitive to Trp starvation, which is inducedin vivoby the host cytokine interferon-γ. In response to Trp starvation, Chlamydia enters a viable but nonreplicating state called persistence. A major characteristic of chlamydial persistence is a block in cell division. We hypothesized that cell division is blocked during persistence by the inability to translate Trp-rich cell division proteins. To test this, we first investigated the translation of various cell division proteins under Trp starvation conditions using inducible expression strains. We observed that the Trp-poor protein MurG and the Trp-neutral protein FtsL were still expressed during persistence, while the expression of the Trp-rich proteins Pbp2, RodA, FtsI/Pbp3, and MraY was significantly reduced. As proof of concept for our hypothesis, we compared expression of a wild-type and mutant isoform of RodZ in which its four Trp codons were mutated. These experiments demonstrated that decreased expression of RodZ during persistence was reversed when no Trp was present in the protein, thus directly linking its expression to its Trp content. Together, these experiments indicate that specific cell division proteins are not produced during persistence. For the first time, our data provide a mechanism that explains the inhibition of cell division during chlamydial persistence mediated by Trp starvation.