The extracellular adherence protein (Eap) of Staphylococcus aureus acts as a proliferation and migration repressing factor that alters the cell morphology of keratinocytes
The extracellular adherence protein (Eap) of Staphylococcus aureus acts as a proliferation and migration repressing factor that alters the cell morphology of keratinocytes
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DOI：
10.1016/j.ijmm.2017.01.002
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发表时间：
2017-01-01
影响因子：
4.1
通讯作者：
Bischoff, Markus
中科院分区：
文献类型：
--
作者：
Eisenbeis, Janina;Peisker, Henrik;Bischoff, Markus
金黄色葡萄球菌是一种主要的人类病原体，也是浅表和深层伤口感染的常见原因。该病原体配备了大量毒力因子，有助于附着于各种真核细胞结构并调节宿主免疫反应。这些因子之一是细胞外粘附蛋白 Eap，它是“分泌性扩展粘附分子”(SERAM) 蛋白家族的成员，具有粘附和免疫调节特性。此前研究表明，这种分泌的蛋白质会通过干扰宿主防御和新血管形成来损害伤口愈合。然而，它对角质形成细胞增殖和迁移（伤口上皮再形成过程中的两个主要步骤）的影响尚不清楚。在这里，我们报告 Eap 通过改变角质形成细胞的形态和粘附特性来影响其增殖和迁移能力。特别是，用 Eap 处理未汇合的 HaCaT 细胞培养物会导致细胞形态变化以及细胞增殖和迁移的显着减少。 Eap处理的HaCaT细胞的外观从长方形经梯形变为星形，伴随着细胞体积和细胞硬度的减小，并表现出显着增加的细胞粘附。 Eap 对内皮细胞和癌细胞具有类似的影响，表明 Eap 对真核细胞形态和功能的总体影响。具体来说，Eap 被发现会干扰生长因子刺激的丝裂原激活蛋白激酶 (MAPK) 途径的激活，已知该途径负责细胞形状调节、诱导上皮细胞增殖和迁移。蛋白质印迹分析显示，Eap 阻断角质形成细胞生长因子 (KGF) 刺激的 HaCaT 细胞中细胞外信号调节激酶 1 和 2 (Erk1/2) 的磷酸化。总之，这些数据增加了 Eap 在伤口愈合中的另一种拮抗机制，即细菌蛋白干扰角质形成细胞迁移和增殖。 (C) 2017 爱思唯尔有限公司。版权所有。
Staphyloccocus aureus is a major human pathogen and a common cause for superficial and deep seated wound infections. The pathogen is equipped with a large arsenal of virulence factors, which facilitate attachment to various eukaryotic cell structures and modulate the host immune response. One of these factors is the extracellular adherence protein Eap, a member of the "secretable expanded repertoire adhesive molecules" (SERAM) protein family that possesses adhesive and immune modulatory properties. The secreted protein was previously shown to impair wound healing by interfering with host defense and neovascularization. However, its impact on keratinocyte proliferation and migration, two major steps in the re-epithelialization process of wounds, is not known. Here, we report that Eap affects the proliferation and migration capacities of keratinocytes by altering their morphology and adhesive properties. In particular, treatment of non-confluent HaCaT cell cultures with Eap resulted in cell morphology changes as well as a significant reduction in cell proliferation and migration. Eap-treated HaCaT cells changed their appearance from an oblong via a trapezoid to an astral-like shape, accompanied by decreases in cell volume and cell stiffness, and exhibited significantly increased cell adhesion. Eap had a similar influence on endothelial and cancer cells, indicative for a general effect of Eap on eukaryotic cell morphology and functions. Specifically, Eap was found to interfere with growth factor-stimulated activation of the mitogen-activated protein kinase (MAPK) pathway that is known to be responsible for cell shape modulation, induction of proliferation and migration of epithelial cells. Western blot analyses revealed that Eap blocked the phosphorylation of extracellular signal-regulated kinase 1 and 2 (Erk1/2) in keratinocyte growth factor (KGF)-stimulated HaCaT cells. Together, these data add another antagonistic mechanism of Eap in wound healing, whereby the bacterial protein interferes with keratinocyte migration and proliferation. (C) 2017 Elsevier GmbH. All rights reserved.