A nasal epithelial receptor for Staphylococcus aureus WTA governs adhesion to epithelial cells and modulates nasal colonization.

A nasal epithelial receptor for Staphylococcus aureus WTA governs adhesion to epithelial cells and modulates nasal colonization.
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DOI:
10.1371/journal.ppat.1004089
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发表时间:
2014-05
期刊:
影响因子:
6.7
通讯作者:
Weidenmaier C
Weidenmaier C
中科院分区:
医学1区
文献类型:
--
作者:
Baur S;Rautenberg M;Faulstich M;Grau T;Severin Y;Unger C;Hoffmann WH;Rudel T;Autenrieth IB;Weidenmaier C

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鼻腔定植是金黄色葡萄球菌感染的主要危险因素。负责定植的机制仍然没有很好地理解,涉及宿主和细菌方面的几个因素。其中一个关键因素是金黄色葡萄球菌的细胞壁壁壁酸(WTA),它控制着与鼻上皮表面的直接相互作用。我们在这里报道了鼻部上皮细胞上细胞壁糖共聚物WTA的第一个受体。在一些实验系统中,这种类型的f清除剂受体,称为sreci,以电荷依赖的方式结合WTA,并介导体外鼻上皮细胞的粘附。在剪切应力下,WTA和sreci相互作用对上皮细胞粘附的影响尤为明显,这与鼻腔中的情况相似。最重要的是,我们在这里证明了wta受体相互作用在棉花大鼠鼻腔定植模型中的关键作用。当我们用sreci抗体抑制WTA介导的粘附时,动物模型中的鼻腔定植在定植开始的早期就明显减少。更重要的是,在延长的6天内,殖民化保持在较低的水平。因此,我们提出靶向这种糖共聚物-受体相互作用作为预防或控制金黄色葡萄球菌鼻腔定植的新策略。大约20%的人口被金黄色葡萄球菌定植。金黄色葡萄球菌的宿主主要是人的鼻子。通常,定植不会导致感染,因此没有症状。然而,当住院患者表现出免疫系统受到抑制时,他们就有被自己的鼻腔金黄色葡萄球菌感染的风险。因此,了解殖民背后的事件和机制是很重要的。到目前为止,金黄色葡萄球菌的鼻腔定植只被部分了解。细菌的一个关键因素是金黄色葡萄球菌的糖聚合物,称为细胞壁壁酸(WTA),它参与了金黄色葡萄球菌粘附在鼻腔内部细胞表面的过程。我们在这里表明,在这些细胞上表达的受体蛋白与WTA结合,从而参与了金黄色葡萄球菌与鼻细胞的粘附。这种机制对动物模型的鼻腔定植有强烈的影响,类似于人类鼻子的情况。最重要的是,在动物模型中,抑制WTA介导的黏附可显著减少鼻腔定植。因此,我们提出靶向这种糖共聚物-受体相互作用可以作为控制金黄色葡萄球菌鼻腔定植的新策略。
Nasal colonization is a major risk factor for S. aureus infections. The mechanisms responsible for colonization are still not well understood and involve several factors on the host and the bacterial side. One key factor is the cell wall teichoic acid (WTA) of S. aureus, which governs direct interactions with nasal epithelial surfaces. We report here the first receptor for the cell wall glycopolymer WTA on nasal epithelial cells. In several assay systems this type F-scavenger receptor, termed SREC-I, bound WTA in a charge dependent manner and mediated adhesion to nasal epithelial cells in vitro. The impact of WTA and SREC-I interaction on epithelial adhesion was especially pronounced under shear stress, which resembles the conditions found in the nasal cavity. Most importantly, we demonstrate here a key role of the WTA-receptor interaction in a cotton rat model of nasal colonization. When we inhibited WTA mediated adhesion with a SREC-I antibody, nasal colonization in the animal model was strongly reduced at the early onset of colonization. More importantly, colonization stayed low over an extended period of 6 days. Therefore we propose targeting of this glycopolymer-receptor interaction as a novel strategy to prevent or control S. aureus nasal colonization. About 20% of the human population is colonized by Staphylococcus aureus. The reservoir of S. aureus is mainly the human nose. Usually, colonization does not lead to infection and is therefore without symptoms. However, when hospitalized patients exhibit a suppressed immune system, they are at risk of getting infected by their own nasal S. aureus strain. Therefore, it is important to understand the events and mechanisms underlying colonization. Until now S. aureus nasal colonization is only partially understood. One bacterial key factor is a sugar polymer of S. aureus, termed cell wall teichoic acid (WTA), which is involved in S. aureus adhesion to cellular surfaces in the inner part of the nasal cavity. We show here that a receptor-protein, which is expressed on such cells, binds WTA and is thereby involved in adhesion of S. aureus to nasal cells. This mechanism has a strong impact on nasal colonization in an animal model that resembles the situation in the human nose. Most importantly, inhibition of WTA mediated adhesion strongly reduces nasal colonization in the animal model. Therefore we propose that targeting of this glycopolymer-receptor interaction could serve as a novel strategy to control S. aureus nasal colonization.
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