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AphB 和 CadC 相互作用激活. 的酸抗性

The Interplay of AphB and CadC to Activate Acid Resistance of .

机构信息

Faculty of Biology: Microbiology, Ludwig-Maximilians-Universität München, Martinsried, Germany.

出版信息

J Bacteriol. 2023 Apr 25;205(4):e0045722. doi: 10.1128/jb.00457-22. Epub 2023 Mar 15.

Abstract

Bacteria have evolved different systems to sense and adapt to acid stress. For example, Vibrio campbellii, a marine pathogen for invertebrates, encounters acidic conditions in the digestive glands of shrimp. The main acid resistance system of is the Cad system, which is activated when cells are in a low-pH, amino acid-rich environment. The Cad system consists of the pH-responsive transcriptional activator CadC, the lysine decarboxylase CadA, and the lysine/cadaverine antiporter CadB. In many species, the LysR-type transcriptional regulator AphB is involved in the regulation of the Cad system, but its precise role is unclear. Here, we examined AphB of and in the context of Cad activation. At low pH, an deletion mutant was less able to grow and survive compared with the wild-type because it did not excrete sufficient alkaline cadaverine to increase the extracellular pH. AphB was found to upregulate the transcription of thereby increasing its protein copy number per cell. Moreover, AphB itself was shown to be a pH-sensor, and binding to the promoter increased under low pH, as shown by surface plasmon resonance spectroscopy. By monitoring the activation of the Cad system over a wide range of pH values, we found that AphB-mediated upregulation of not only adjusts CadC copy numbers depending on acid stress strength, but also affects the response of individual cells and thus the degree of heterogeneous Cad system activation in the population. Acid resistance is an important property not only for neutralophilic enteric bacteria such as Escherichia, , and Salmonella, but also for . To counteract acidic threats, the marine Vibrio campbellii, a pathogen for various invertebrates, activates the acid-resistance Cad system. The transcriptional activator of the Cad system is CadC, an extracellular pH-sensor. The expression of is upregulated by the transcriptional regulator AphB to achieve maximum expression of the components of the Cad system. studies demonstrate that AphB binds more tightly to the DNA under low pH. The interplay of two pH-responsive transcriptional activators allows tight control of the activity of the Cad system.

摘要

细菌已经进化出不同的系统来感知和适应酸性应激。例如,海洋无脊椎动物病原体坎贝尔弧菌,在虾的消化腺中遇到酸性环境。 的主要抗酸系统是 Cad 系统,当细胞处于低 pH 值、富含氨基酸的环境中时,该系统被激活。Cad 系统由 pH 响应转录激活因子 CadC、赖氨酸脱羧酶 CadA 和赖氨酸/尸胺反向转运蛋白 CadB 组成。在许多 物种中,LysR 型转录调节因子 AphB 参与 Cad 系统的调节,但它的确切作用尚不清楚。在这里,我们研究了 Cad 激活背景下的 和 的 AphB。在低 pH 值下,与野生型相比, 缺失突变体的生长和存活能力较差,因为它不能分泌足够的碱性尸胺来增加细胞外 pH 值。发现 AphB 上调 的转录,从而增加每个细胞的蛋白拷贝数。此外,发现 AphB 本身是一个 pH 传感器,在低 pH 值下,它与 启动子的结合增加,这一点通过表面等离子体共振光谱得到证实。通过在广泛的 pH 值范围内监测 Cad 系统的激活,我们发现 AphB 介导的 上调不仅根据酸应激强度调节 CadC 拷贝数,还影响单个细胞的反应,从而影响 群体中 Cad 系统激活的异质性程度。抗酸性不仅是嗜中性肠道细菌(如大肠杆菌、、沙门氏菌)的重要特性,也是 的重要特性。为了对抗酸性威胁,各种无脊椎动物病原体海洋弧菌激活了抗酸 Cad 系统。Cad 系统的转录激活因子是 CadC,它是一种细胞外 pH 传感器。转录调节因子 AphB 上调 的表达,以实现 Cad 系统组件的最大表达。 研究表明,AphB 在低 pH 值下与 DNA 结合更紧密。两种 pH 响应转录激活因子的相互作用允许对 Cad 系统的活性进行严格控制。

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