Wall Teichoic Acids Facilitate the Release of Toxins from the Surface of Staphylococcus aureus.
Wall Teichoic Acids Facilitate the Release of Toxins from the Surface of Staphylococcus aureus.
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DOI：
10.1128/spectrum.01011-22
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发表时间：
2022-08-31
影响因子：
3.7
通讯作者：
Masseya, Ruth C.
中科院分区：
文献类型：
--
作者：
Brignoli, Tarcisio;Douglas, Edward;Duggan, Seana;Fagunloye, Olayemi Grace;Adhikari, Rajan;Aman, M. Javad;Masseya, Ruth C.
金黄色葡萄球菌致病性的一个主要特征是其分泌溶细胞毒素的能力。这个过程涉及毒素从细胞质通过细菌膜和细胞壁转移到外部环境。它们通过膜的运动过程相对明确，涉及一般和毒素特异性分泌系统。毒素通过细胞壁的运动被认为涉及蛋白质通过多孔细胞壁结构的被动扩散;然而，最近的工作表明，这是更复杂的，在这里，我们证明了壁磷壁酸（WTA）在这个过程中的作用。利用全基因组关联的方法，我们确定了一个多态性的基因座编码的WTA生物合成机制与溶细胞活性的细菌。我们使用同基因突变体集验证了这种关联，并发现WTA是从细菌细胞释放几种溶细胞毒素所必需的。我们表明，这种效果是介导的变化，在整个细胞的信封，结果从WTA的损失的静电荷。作为开发新疗法的主要目标，重要的是我们充分了解溶细胞毒素产生和释放的整个过程。这些发现为人类主要病原体的毒素释放过程开辟了一个新的方面，同时也证明临床分离株可以利用WTA的产生来改变其细胞毒性，从而改变其致病能力。细胞溶解毒素的产生和释放是许多细菌病原体致病性的关键方面。在这项研究中，我们证明了壁磷壁酸的作用，锚定在细菌细胞壁的肽聚糖的分子，在毒素从S。金黄色葡萄球菌细胞进入细胞外环境。我们的研究结果表明，这种效应是介导的静电荷梯度的存在下，带负电荷的WTA分子创建跨细胞包膜。这项工作为我们理解S.金黄色葡萄球菌，并证明了这种主要的人类病原体可以适应其致病能力的进一步手段。
A major feature of the pathogenicity of Staphylococcus aureus is its ability to secrete cytolytic toxins. This process involves the translocation of the toxins from the cytoplasm through the bacterial membrane and the cell wall to the external environment. The process of their movement through the membrane is relatively well defined, involving both general and toxin-specific secretory systems. Movement of the toxins through the cell wall was considered to involve the passive diffusion of the proteins through the porous cell wall structures; however, recent work suggests that this is more complex, and here we demonstrate a role for the wall teichoic acids (WTA) in this process. Utilizing a genome-wide association approach, we identified a polymorphism in the locus encoding the WTA biosynthetic machinery as associated with the cytolytic activity of the bacteria. We verified this association using an isogenic mutant set and found that WTA are required for the release of several cytolytic toxins from the bacterial cells. We show that this effect is mediated by a change in the electrostatic charge across the cell envelope that results from the loss of WTA. As a major target for the development of novel therapeutics, it is important that we fully understand the entire process of cytolytic toxin production and release. These findings open up a new aspect to the process of toxin release by a major human pathogen while also demonstrating that clinical isolates can utilize WTA production to vary their cytotoxicity, thereby altering their pathogenic capabilities. IMPORTANCE The production and release of cytolytic toxins is a critical aspect for the pathogenicity of many bacterial pathogens. In this study, we demonstrate a role for wall teichoic acids, molecules that are anchored to the peptidoglycan of the bacterial cell wall, in the release of toxins from S. aureus cells into the extracellular environment. Our findings suggest that this effect is mediated by a gradient of electrostatic charge which the presence of the negatively charged WTA molecules create across the cell envelope. This work brings an entirely new aspect to our understanding of the cytotoxicity of S. aureus and demonstrates a further means by which this major human pathogen can adapt its pathogenic capabilities.
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影响因子：
3.2
作者：
D'Elia, Michael A.;Henderson, James A.;Brown, Eric D.
通讯作者：
Brown, Eric D.
DOI：
10.1073/pnas.1004304107
发表时间：
2010-11-02
影响因子：
11.1
作者：
Atilano, Magda L.;Pereira, Pedro M.;Filipe, Sergio R.
通讯作者：
Filipe, Sergio R.
影响因子：
3.2
作者：
Grundling, Angelika;Schneewind, Olaf
通讯作者：
Schneewind, Olaf
影响因子：
3.1
作者：
Koprivnjak, Tomaz;Weidenmaier, Christopher;Weiss, Jerrold P.
通讯作者：
Weiss, Jerrold P.
影响因子：
0.8
作者：
Kho, Kelvin;Meredith, Timothy C.
通讯作者：
Meredith, Timothy C.