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衣原体转录调控因子 Euo 是细胞形态发育进程中的关键开关,但不参与形成感染形式的决定性步骤。

The chlamydial transcriptional regulator Euo is a key switch in cell form developmental progression but is not involved in the committed step to the formation of the infectious form.

机构信息

Department of Biological Sciences, University of Idaho, Moscow, Idaho, USA.

Paul G. Allen School For Global Health, Washington State University, Pullman, Washington, USA.

出版信息

mSphere. 2024 Sep 25;9(9):e0043724. doi: 10.1128/msphere.00437-24. Epub 2024 Aug 14.

DOI:10.1128/msphere.00437-24
PMID:39140730
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11423577/
Abstract

UNLABELLED

Bacteria in the genus are a significant health burden worldwide. They infect a wide range of vertebrate animals, including humans and domesticated animals. In humans, can cause zoonotic pneumonia, while causes a variety of respiratory infections. Infections with cause ocular or genital infections. All chlamydial species are obligate intracellular bacteria that replicate exclusively inside of eukaryotic host cells. Chlamydial infections are dependent on a complex infection cycle that depends on transitions between specific cell forms. This cycle consists of cell forms specialized for host cell invasion, the elementary body (EB), and a form specialized for intracellular replication, the reticulate body (RB). In addition to the EB and RB, there is a transitionary cell form that mediates the transformation between the RB and the EB, the intermediate body (IB). In this study, we ectopically expressed the regulatory protein Euo and showed that high levels of expression resulted in reversible arrest of the development cycle. The arrested chlamydial cells were trapped phenotypically at an early IB stage of the cycle. These cells had exited the cell cycle but had not shifted gene expression from RB like to IB/EB like. This arrested state was dependent on continued expression of Euo. When ectopic expression was reversed, Euo levels dropped in the arrested cells which led to the repression of native Euo expression and the resumption of the developmental cycle. Our data are consistent with a model where Euo expression levels impact IB maturation to the infectious EB but not the production of the IB form.

IMPORTANCE

Bacterial species in the Chlamydiales order infect a variety of vertebrate animals and are a global health concern. They cause various diseases in humans, including genital and respiratory infections. The bacteria are obligate intracellular parasites that rely on a complex infectious cycle involving multiple cell forms. All species share the same life cycle, transitioning through different states to form the infectious elementary body (EB) to spread infections to new hosts. The Euo gene, encoding a DNA-binding protein, is involved in regulating this cycle. This study showed that ectopic expression of Euo halted the cycle at an early stage. This arrest depended on continued Euo expression. When Euo expression was reversed, the developmental cycle resumed. Additionally, this study suggests that high levels of Euo expression affect the formation of the infectious EB but not the production of the cell form committed to EB formation.

摘要

未加标签

属细菌是全球范围内的重大健康负担。它们感染范围广泛的脊椎动物,包括人类和家畜。在人类中,可引起人畜共患性肺炎,而 引起多种呼吸道感染。感染 引起眼部或生殖器感染。所有衣原体物种都是专性细胞内细菌,仅在真核宿主细胞内复制。衣原体感染依赖于一个复杂的感染周期,该周期依赖于特定细胞形式之间的转变。该周期由专门用于宿主细胞入侵的细胞形式、原始体 (EB) 和专门用于细胞内复制的形式、网状体 (RB) 组成。除了 EB 和 RB 之外,还有一种过渡细胞形式,介导 RB 和 EB 之间的转化,即中间体 (IB)。在这项研究中,我们异位表达了调节蛋白 Euo,并表明高水平的表达导致发育周期的可逆停滞。被捕获的衣原体细胞在周期的早期 IB 阶段被捕获表型。这些细胞已经退出细胞周期,但尚未从 RB 样基因表达转变为 IB/EB 样基因表达。这种被捕获的状态依赖于 Euo 的持续表达。当异位表达被逆转时,Euo 水平在被捕获的细胞中下降,导致内源性 Euo 表达的抑制和发育周期的恢复。我们的数据与以下模型一致,即 Euo 的表达水平影响 IB 向感染性 EB 的成熟,但不影响 IB 形式的产生。

重要性

衣原体目中的细菌物种感染多种脊椎动物,是全球健康关注的问题。它们在人类中引起各种疾病,包括生殖器和呼吸道感染。这些细菌是专性细胞内寄生虫,依赖于一个复杂的感染周期,涉及多种细胞形式。所有物种都具有相同的生命周期,通过不同的状态过渡形成感染性原始体 (EB),从而将感染传播给新的宿主。编码 DNA 结合蛋白的 Euo 基因参与调节这个周期。本研究表明,Euo 的异位表达使周期在早期停滞。这种捕获依赖于 Euo 的持续表达。当 Euo 表达被逆转时,发育周期恢复。此外,这项研究表明,高水平的 Euo 表达影响感染性 EB 的形成,但不影响形成专用于 EB 形成的细胞形式。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9abf/11423577/47ee8b236f93/msphere.00437-24.f008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9abf/11423577/5952f37751b9/msphere.00437-24.f005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9abf/11423577/cfe41f4168e5/msphere.00437-24.f006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9abf/11423577/a2375ed30bce/msphere.00437-24.f007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9abf/11423577/47ee8b236f93/msphere.00437-24.f008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9abf/11423577/a4e8eb47ffd9/msphere.00437-24.f001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9abf/11423577/d05f7d995e4a/msphere.00437-24.f002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9abf/11423577/685addfca936/msphere.00437-24.f003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9abf/11423577/3bb00056f5af/msphere.00437-24.f004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9abf/11423577/5952f37751b9/msphere.00437-24.f005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9abf/11423577/cfe41f4168e5/msphere.00437-24.f006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9abf/11423577/a2375ed30bce/msphere.00437-24.f007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9abf/11423577/47ee8b236f93/msphere.00437-24.f008.jpg

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Gene gain facilitated endosymbiotic evolution of Chlamydiae.基因获得促进了衣原体的内共生进化。
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