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应激反应蛋白 BolA 影响沙门氏菌 Typhimurium 的适应性并促进其毒力。

Stress Response Protein BolA Influences Fitness and Promotes Salmonella enterica Serovar Typhimurium Virulence.

机构信息

Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Universidade de Lisboa, Lisbon, Portugal.

Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Oeiras, Portugal.

出版信息

Appl Environ Microbiol. 2018 Apr 2;84(8). doi: 10.1128/AEM.02850-17. Print 2018 Apr 15.

Abstract

The intracellular pathogen serovar Typhimurium has emerged as a major cause of foodborne illness, representing a severe clinical and economic concern worldwide. The capacity of this pathogen to efficiently infect and survive inside the host depends on its ability to synchronize a complex network of virulence mechanisms. Therefore, the identification of new virulence determinants has become of paramount importance in the search of new targets for drug development. BolA-like proteins are widely conserved in all kingdoms of life. In , this transcription factor has a critical regulatory role in several mechanisms that are tightly related to bacterial virulence. Therefore, in the present work we used the well-established infection model to evaluate the role of BolA protein in Typhimurium virulence. We have shown that BolA is an important player in Typhimurium pathogenesis. Specifically, the absence of BolA leads to a defective virulence capacity that is most likely related to the remarkable effect of this protein on Typhimurium evasion of the cellular response. Furthermore, it was demonstrated that BolA has a critical role in bacterial survival under harsh conditions since BolA conferred protection against acidic and oxidative stress. Hence, we provide evidence that BolA is a determining factor in the ability of to survive and overcome host defense mechanisms, and this is an important step in progress to an understanding of the pathways underlying bacterial virulence. BolA has been described as an important protein for survival in the late stages of bacterial growth and under harsh environmental conditions. High levels of BolA in stationary phase and under stresses have been connected with a plethora of phenotypes, strongly suggesting its important role as a master regulator. Here, we show that BolA is a determining factor in the ability of to survive and overcome host defense mechanisms, and this is an important step in progress to an understanding of the pathways underlying bacterial virulence. This work constitutes a relevant step toward an understanding of the role of BolA protein and may have an important impact on future studies in other organisms. Therefore, this study is of utmost importance for understanding the genetic and molecular bases involved in the regulation of virulence and may contribute to future industrial and public health care applications.

摘要

肠道病原体鼠伤寒血清型已成为食源性疾病的主要原因,是全球范围内严重的临床和经济问题。该病原体在宿主内部高效感染和存活的能力取决于其同步复杂毒力机制网络的能力。因此,确定新的毒力决定因素对于寻找药物开发的新靶点变得至关重要。BolA 样蛋白在所有生命领域都广泛保守。在 中,这种转录因子在与细菌毒力紧密相关的几种机制中具有关键的调控作用。因此,在本工作中,我们使用成熟的感染模型 来评估 BolA 蛋白在鼠伤寒血清型毒力中的作用。我们表明 BolA 是鼠伤寒血清型发病机制中的重要参与者。具体来说,BolA 的缺失导致毒力能力缺陷,这很可能与该蛋白对鼠伤寒逃避细胞反应的显著影响有关。此外,还证明了 BolA 在细菌在恶劣条件下的存活中具有关键作用,因为 BolA 赋予了对酸性和氧化应激的保护。因此,我们提供的证据表明 BolA 是 生存和克服宿主防御机制的决定因素,这是理解细菌毒力潜在途径的重要一步。BolA 已被描述为细菌在生长后期和恶劣环境条件下生存的重要蛋白。在静止期和应激下高水平的 BolA 与多种表型相关联,强烈表明其作为主调控因子的重要作用。在这里,我们表明 BolA 是 生存和克服宿主防御机制的决定因素,这是理解细菌毒力潜在途径的重要一步。这项工作是理解 BolA 蛋白作用的重要一步,可能对其他生物体的未来研究产生重要影响。因此,这项研究对于理解参与调节 毒力的遗传和分子基础具有重要意义,并可能为未来的工业和公共卫生保健应用做出贡献。

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