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VirAB ABC 转运蛋白是李斯特菌毒力和耐乳链菌肽的 VirR 调控所必需的。

The VirAB ABC Transporter Is Required for VirR Regulation of Listeria monocytogenes Virulence and Resistance to Nisin.

机构信息

Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA.

Aduro Biotech, Berkeley, California, USA.

出版信息

Infect Immun. 2018 Feb 20;86(3). doi: 10.1128/IAI.00901-17. Print 2018 Mar.

Abstract

is a Gram-positive intracellular pathogen that causes a severe invasive disease. Upon infecting a host cell, upregulates the transcription of numerous factors necessary for productive infection. VirR is the response regulator component of a two-component regulatory system in In this report, we have identified the putative ABC transporter encoded by genes as necessary for VirR function. We have designated We constructed an in-frame deletion of and determined that the Δ mutant exhibited reduced transcription of VirR-regulated genes. The Δ mutant also showed defects in plaque formation and virulence that were similar to those of a Δ deletion mutant. Since VirR is important for innate resistance to antimicrobial agents, we determined the MICs of nisin and bacitracin for Δ bacteria. We found that VirAB expression was necessary for nisin resistance but was dispensable for resistance to bacitracin. This result suggested a VirAB-independent mechanism of VirR regulation in response to bacitracin. Lastly, we found that the Δ and Δ mutants had no deficiency in growth in broth culture, intracellular replication, or production of the ActA surface protein, which facilitates actin-based motility and cell-to-cell spread. However, the Δ and Δ mutants produced shorter actin tails during intracellular infection, which suggested that these mutants have a reduced ability to move and spread via actin-based motility. These findings have demonstrated that VirAB functions in a pathway with VirR to regulate the expression of genes necessary for virulence and resistance to antimicrobial agents.

摘要

是一种革兰氏阳性细胞内病原体,可引起严重的侵袭性疾病。在感染宿主细胞后,上调许多对有效感染必需的转录因子。VirR 是 中双组分调控系统的应答调节子成分。在本报告中,我们鉴定了编码基因的假定 ABC 转运蛋白是 VirR 功能所必需的。我们将其命名为 。我们构建了一个基因的框内缺失突变体,并确定该 Δ 突变体表现出 VirR 调节基因转录的减少。Δ 突变体还表现出在 噬菌斑形成和毒力方面的缺陷,类似于 Δ 缺失突变体。由于 VirR 对天然抗微生物剂的抗性很重要,我们确定了 Δ 细菌对乳链菌肽和杆菌肽的 MIC。我们发现 VirAB 表达对于乳链菌肽抗性是必需的,但对于杆菌肽抗性是可有可无的。这一结果表明,VirR 对杆菌肽的响应存在一种 VirAB 非依赖性的调控机制。最后,我们发现 Δ 和 Δ 突变体在肉汤培养物中生长、细胞内复制或 ActA 表面蛋白的产生方面没有缺陷,ActA 表面蛋白促进肌动蛋白依赖的运动和细胞间传播。然而,Δ 和 Δ 突变体在细胞内感染期间产生的肌动蛋白尾巴较短,这表明这些突变体在通过肌动蛋白依赖的运动进行运动和传播方面的能力降低。这些发现表明, 在与 VirR 一起的途径中发挥作用,以调节毒力和抗微生物剂抗性所必需的基因表达。

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