Departamento de Ciencias Biológicas, Facultad de Ciencias Exactas, Instituto de Biotecnología y Biología Molecular (IBBM)-CCT-CONICET-La Plata, Universidad Nacional de La Plata, La Plata, Argentina.
Department of Microbiology, Immunology, and Cell Biology, Vaccine Development Center at West Virginia University Health Sciences Center, Morgantown, West Virginia, USA.
Microbiol Spectr. 2024 Nov 5;12(11):e0079424. doi: 10.1128/spectrum.00794-24. Epub 2024 Oct 4.
is a pathogenic bacterium that causes respiratory infections in mammals. Adhesins, toxins, and secretion systems necessary for infection are regulated by the two-component system BvgAS. When the BvgAS system is inactive, there is no transcription of virulence-activated genes, and virulence-repressed genes () are expressed. The regulation of some in is dependent upon the virulence-activated gene . Although having a regulatory role, no DNA-binding domain is described for BvgR. Instead, it contains an EAL domain, usually found in cyclic-di-GMP (c-di-GMP)-specific phosphodiesterases. c-di-GMP is a bacterial second messenger that regulates multiple phenotypes in bacteria, including . The current study aimed to deepen our knowledge about BvgR. We employed RNA-seq analysis to define the BvgR regulon, and then we investigated the phenotypes in which BvgR regulation might be involved such as biofilm formation, cytotoxicity, and virulence. Our result revealed that BvgR inhibits biofilm formation and flagellin expression in virulent phase. Although BvgR has long been considered a repressor protein, our results show that it also upregulates almost 100 genes. This regulation is likely indirect, as BvgR lacks a DNA-binding domain. Notably, among the upregulated genes, we identified 15 associated with the type three secretion system. Consistent with these findings, a strain deficient in was less cytotoxic than the wild-type strain, elicited a milder immune response, and was less able to persist in the lower respiratory tract of mice.IMPORTANCE is a harmful bacterium responsible for respiratory infections in mammals. Its ability to cause disease is tightly regulated by a system called BvgAS. In this study, we focused on understanding the role of a specific gene called in regulating 's virulence factors. Our findings revealed that BvgR, previously thought to primarily repress gene expression, actually plays a complex role in both activating and inhibiting various genes involved in bacterial virulence. This newfound understanding sheds light on the intricate mechanisms underlying 's ability to cause infections, providing valuable insights for developing strategies to combat these infections in humans and animals.
是一种能引起哺乳动物呼吸道感染的病原菌。黏附素、毒素和分泌系统等感染所必需的物质是由双组分系统 BvgAS 调节的。当 BvgAS 系统处于非激活状态时，毒力激活基因没有转录，而毒力抑制基因()被表达。的一些基因的调节取决于毒力激活基因。虽然 BvgR 具有调节作用，但它没有 DNA 结合结构域。相反，它包含一个 EAL 结构域，通常存在于环二鸟苷酸（c-di-GMP）特异性磷酸二酯酶中。c-di-GMP 是一种细菌第二信使，可调节细菌的多种表型，包括。本研究旨在加深我们对 BvgR 的了解。我们采用 RNA-seq 分析来定义 BvgR 调控组，然后研究 BvgR 调节可能涉及的表型，如生物膜形成、细胞毒性和毒力。我们的结果表明，BvgR 抑制了毒力相生物膜的形成和鞭毛蛋白的表达。尽管 BvgR 长期以来被认为是一种阻遏蛋白，但我们的结果表明它还上调了近 100 个基因。这种调节可能是间接的，因为 BvgR 缺乏 DNA 结合结构域。值得注意的是，在上调的基因中，我们鉴定出 15 个与 III 型分泌系统相关的基因。与这些发现一致的是，缺失的菌株比野生型菌株的细胞毒性更小，引起的免疫反应更温和，并且在小鼠下呼吸道的持续存在能力更差。
重要的是，是一种能引起哺乳动物呼吸道感染的有害细菌。其致病能力受到一个名为 BvgAS 的系统的严格调节。在这项研究中，我们重点研究了一个名为的特定基因在调节细菌毒力因子方面的作用。我们的研究结果表明，以前被认为主要起抑制基因表达作用的 BvgR，实际上在激活和抑制与细菌毒力相关的各种基因方面发挥着复杂的作用。这一新的认识揭示了细菌感染能力背后的复杂机制，为开发针对人类和动物感染的策略提供了有价值的见解。
