Singh Vandana, Ouellette Scot P
Department of Pathology, Microbiology, and Immunology, College of Medicine, University of Nebraska Medical Center, Omaha, United States.
Elife. 2025 Jan 17;13:RP98409. doi: 10.7554/eLife.98409.
is an obligate intracellular bacterial pathogen with a unique developmental cycle. It differentiates between two functional and morphological forms: the elementary body (EB) and the reticulate body (RB). The signals that trigger differentiation from one form to the other are unknown. EBs and RBs have distinctive characteristics that distinguish them, including their size, infectivity, proteome, and transcriptome. Intriguingly, they also differ in their overall redox status as EBs are oxidized and RBs are reduced. We hypothesize that alterations in redox may serve as a trigger for secondary differentiation. To test this, we examined the function of the primary antioxidant enzyme alkyl hydroperoxide reductase subunit C (AhpC), a well-known member of the peroxiredoxins family, in chlamydial growth and development. Based on our hypothesis, we predicted that altering the expression of would modulate chlamydial redox status and trigger earlier or delayed secondary differentiation. Therefore, we created overexpression and knockdown strains. During knockdown, ROS levels were elevated, and the bacteria were sensitive to a broad set of peroxide stresses. Interestingly, we observed increased expression of EB-associated genes and concurrent higher production of EBs at an earlier time in the developmental cycle, indicating earlier secondary differentiation occurs under elevated oxidation conditions. In contrast, overexpression of AhpC created a resistant phenotype against oxidizing agents and delayed secondary differentiation. Together, these results indicate that redox potential is a critical factor in developmental cycle progression. For the first time, our study provides a mechanism of chlamydial secondary differentiation dependent on redox status.
是一种具有独特发育周期的专性细胞内细菌病原体。它可分化为两种功能和形态形式：原体（EB）和网状体（RB）。触发从一种形式向另一种形式分化的信号尚不清楚。EB和RB具有使其相互区别的独特特征，包括它们的大小、感染性、蛋白质组和转录组。有趣的是，它们的整体氧化还原状态也有所不同，因为EB被氧化而RB被还原。我们假设氧化还原的改变可能作为二次分化的触发因素。为了验证这一点，我们研究了主要抗氧化酶烷基过氧化氢还原酶亚基C（AhpC），过氧化物氧还蛋白家族的一个知名成员，在衣原体生长和发育中的功能。基于我们的假设，我们预测改变AhpC的表达会调节衣原体的氧化还原状态并触发早期或延迟的二次分化。因此，我们构建了AhpC过表达和敲低菌株。在AhpC敲低期间，活性氧水平升高，细菌对多种过氧化物应激敏感。有趣的是，我们观察到在发育周期的早期，EB相关基因的表达增加以及EB的同时产量更高，表明在氧化条件升高的情况下会发生更早的二次分化。相反，AhpC的过表达产生了对氧化剂的抗性表型并延迟了二次分化。总之，这些结果表明氧化还原电位是发育周期进程中的一个关键因素。我们的研究首次提供了一种依赖于氧化还原状态的衣原体二次分化机制。
