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LysR 转录调节因子对单核细胞增生李斯特菌毒力的贡献及其调控基因的鉴定。

Contributions of a LysR Transcriptional Regulator to Listeria monocytogenes Virulence and Identification of Its Regulons.

机构信息

Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, Mississippi, USA

Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, Mississippi, USA.

出版信息

J Bacteriol. 2020 Apr 27;202(10). doi: 10.1128/JB.00087-20.

DOI:10.1128/JB.00087-20
PMID:32179628
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7186455/
Abstract

The capacity of to adapt to environmental changes is facilitated by a large number of regulatory proteins encoded by its genome. Among these proteins are the uncharacterized LysR-type transcriptional regulators (LTTRs). LTTRs can work as positive and/or negative transcription regulators at both local and global genetic levels. Previously, our group determined by comparative genome analysis that one member of the LTTRs (NCBI accession no. WP_003734782) was present in pathogenic strains but absent from nonpathogenic strains. The goal of the present study was to assess the importance of this transcription factor in the virulence of strain F2365 and to identify its regulons. An strain lacking (the F2365Δ strain) displayed significant reductions in cell invasion of and adhesion to Caco-2 cells. In plaque assays, the deletion of resulted in a 42.86% decrease in plaque number and a 13.48% decrease in average plaque size. Furthermore, the deletion of also attenuated the virulence of in mice following oral and intraperitoneal inoculation. The analysis of transcriptomics revealed that the transcript levels of 139 genes were upregulated, while 113 genes were downregulated in the F2365Δ strain compared to levels in the wild-type bacteria. -repressed genes included ABC transporters, important for starch and sucrose metabolism as well as glycerolipid metabolism, flagellar assembly, quorum sensing, and glycolysis/gluconeogenesis. Conversely, activated the expression of genes related to fructose and mannose metabolism, cationic antimicrobial peptide (CAMP) resistance, and beta-lactam resistance. These data suggested that contributed to virulence by broad impact on multiple pathways of gene expression. is the causative agent of listeriosis, an infectious and fatal disease of animals and humans. In this study, we have shown that contributes to pathogenesis and replication in cell lines. We also highlight the importance of in regulating the transcription of genes involved in different pathways that might be essential for the growth and persistence of in the host or under nutrient limitation. Better understanding pathogenesis and the role of various virulence factors is necessary for further development of prevention and control strategies.

摘要

的基因组编码了大量的调控蛋白,这使得它能够适应环境变化。其中包括未被描述的 LysR 型转录调控因子(LTTRs)。LTTRs 可以在局部和全局遗传水平上作为正调控因子和/或负调控因子发挥作用。之前,我们的研究小组通过比较基因组分析发现,LTTRs 的一个成员(NCBI 登录号 WP_003734782)存在于致病菌株中,但不存在于非致病菌株中。本研究的目的是评估该转录因子在 F2365 菌株毒力中的重要性,并鉴定其调控网络。缺失 (F2365Δ 菌株)的 菌株对 Caco-2 细胞的侵袭和黏附能力显著降低。在菌斑试验中,缺失 导致菌斑数量减少 42.86%,平均菌斑大小减少 13.48%。此外,缺失 还减弱了 经口服和腹腔接种后在小鼠中的毒力。转录组学分析显示,与野生型细菌相比,F2365Δ 菌株中 139 个基因的转录水平上调,113 个基因的转录水平下调。- 抑制的基因包括 ABC 转运蛋白,这些基因对淀粉和蔗糖代谢以及甘油脂质代谢、鞭毛组装、群体感应和糖酵解/糖异生很重要。相反, 激活了与果糖和甘露糖代谢、阳离子抗菌肽(CAMP)抗性和β-内酰胺抗性相关的基因的表达。这些数据表明, 通过对多个基因表达途径的广泛影响,有助于 毒力的发挥。 是李斯特菌病的病原体,这是一种动物和人类的传染性和致命疾病。在本研究中,我们已经表明 有助于细胞系中的 发病机制和复制。我们还强调了 在调节参与不同途径的基因转录中的重要性,这些途径可能对 在宿主中或在营养限制下的生长和持续存在至关重要。更好地了解 发病机制和各种毒力因子的作用对于进一步制定预防和控制策略是必要的。

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