Chronic wounds have been considered as major medical problems that may result in expensive healthcare. One of the common causes of chronic wounds is bacterial contamination that leads to persistent inflammation and unbalanced host cell immune responses. Among the bacterial strains that have been identified from chronic wounds, Staphylococcus aureus is the most common strain. We previously observed that S. aureus impaired mouse cutaneous wound healing by delaying re-epithelialization. Here, we investigated the mechanism of delayed re-epithelialization caused by S. aureus infection. With the presence of S. aureus exudate, the migration of in vitro cultured human keratinocytes was significantly inhibited and connexin-43 (Cx43) was upregulated. Inhibition of keratinocyte migration by S. aureus exudate disappeared in keratinocytes where the expression of Cx43 knocked down. Protein kinase phosphorylation array showed that phosphorylation of Akt-S473 was upregulated by S. aureus exudate. In vivo study of Cx43 in S. aureus-infected murine splinted cutaneous wound model showed upregulation of Cx43 in the migrating epithelial edge by S. aureus infection. Treatment with a PI3K/Akt inhibitor reduced Cx43 expression and overcame the wound closure impairment by S. aureus infection in the mouse model. This may contribute to the development of treatment to bacterium-infected wounds.

中文翻译：

---

金黄色葡萄球菌通过激活角质形成细胞中间隙连接蛋白 connexin-43 的表达来损害皮肤伤口愈合。


慢性伤口被认为是可能导致昂贵的医疗费用的主要医疗问题。慢性伤口的常见原因之一是细菌污染，导致持续炎症和不平衡的宿主细胞免疫反应。在已从慢性伤口中鉴定出的细菌菌株中，金黄色葡萄球菌是最常见的菌株。我们之前观察到金黄色葡萄球菌通过延迟再上皮化来损害小鼠皮肤伤口愈合。在这里，我们研究了金黄色葡萄球菌感染引起的延迟再上皮化的机制。金黄色葡萄球菌渗出液的存在，体外培养的人角质形成细胞的迁移受到显着抑制，并且连接蛋白43（Cx43）上调。在 Cx43 表达被敲低的角质形成细胞中，金黄色葡萄球菌渗出物对角质形成细胞迁移的抑制作用消失。蛋白激酶磷酸化芯片显示，Akt-S473 的磷酸化被金黄色葡萄球菌渗出物上调。在金黄色葡萄球菌感染的小鼠夹板皮肤伤口模型中进行的 Cx43 体内研究表明，金黄色葡萄球菌感染导致迁移上皮边缘的 Cx43 上调。在小鼠模型中，使用 PI3K/Akt 抑制剂治疗可降低 Cx43 表达，并克服金黄色葡萄球菌感染造成的伤口闭合损伤。这可能有助于开发细菌感染伤口的治疗方法。