Abstract:
Bacteria in the genus Chlamydia are a significant health burden worldwide. They infect a wide range of vertebrate animals, including humans and domesticated animals. In humans, C. psittaci can cause zoonotic pneumonia, while C. pneumoniae causes a variety of respiratory infections. Infections with C. trachomatis 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.
OBJECTIVE: 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:
衣原体属中的细菌是世界范围内的重大健康负担。它们感染了各种各样的脊椎动物,包括人类和家养动物。在人类中,C.鹦鹉可引起人畜共患肺炎,而肺炎衣原体引起多种呼吸道感染。沙眼衣原体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。衣原体感染取决于复杂的感染周期,该周期取决于特定细胞形式之间的转换。这个周期由专门用于宿主细胞入侵的细胞形式组成,基本体(EB),一种专门用于细胞内复制的形式,网状体(RB)。除了EB和RB,有一个过渡细胞形式,介导RB和EB之间的转换,中间体(IB)。在这项研究中,我们异位表达了调节蛋白Euo,并显示高水平的表达导致发育周期的可逆停滞。被捕的衣原体细胞在周期的早期IB阶段被表型捕获。这些细胞已经退出细胞周期,但没有将基因表达从RB样转变为IB/EB样。这种被逮捕的状态取决于Euo的持续表达。当异位表达反转时,被捕细胞中的Euo水平下降,导致本地Euo表达受到抑制并恢复了发育周期。我们的数据与Euo表达水平影响IB成熟至感染性EB但不影响IB形式的产生的模型一致。
目的:衣原体中的细菌种类感染多种脊椎动物,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。细菌是专性细胞内寄生虫,依赖于涉及多种细胞形式的复杂感染周期。所有物种都有相同的生命周期,通过不同的状态过渡以形成传染性基本体(EB),从而将感染传播到新的宿主。Euo基因,编码DNA结合蛋白,参与调节这个周期。这项研究表明,Euo的异位表达在早期停止了循环。这次逮捕取决于Euo的持续表达。当Euo表达被逆转时,发育周期恢复了。此外,这项研究表明,高水平的Euo表达影响感染性EB的形成,但不影响致力于EB形成的细胞形式的产生。