New Evidence and Insights on Dalbavancin and Wound Healing in a Mouse Model of Skin Infection
New Evidence and Insights on Dalbavancin and Wound Healing in a Mouse Model of Skin Infection
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DOI：
10.1128/aac.02062-19
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发表时间：
2020-04-01
影响因子：
4.9
通讯作者：
Cirioni, Oscar
中科院分区：
文献类型：
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作者：
Simonetti, Oriana;Lucarini, Guendalina;Cirioni, Oscar
Dalbavancin是一种有效的抗生素，广泛用于治疗皮肤感染。我们的目的是确定dalbavancin给药与万古霉素相比对伤口愈合的影响，并阐明表皮生长因子受体（EGFR）、基质金属蛋白酶1 （MMP-1）、MMP-9和血管内皮生长因子（VEGF）是否参与其治疗机制。建立耐甲氧西林金黄色葡萄球菌（MRSA）皮肤感染小鼠模型。小鼠每天服用万古霉素（10 mg/kg），第1天（20 mg/kg）和第8天（10 mg/kg）每周服用达尔巴万辛。14天后，切除伤口，进行细菌计数。通过组织和免疫组织化学染色评估伤口愈合情况，然后进行蛋白质提取和免疫印迹。我们的微生物学结果证实，达巴万辛和万古霉素都能有效地减少伤口的细菌负荷。与未治疗的感染动物和万古霉素治疗组相比，达巴万辛组表现出较强的效果。dalbavancin处理的伤口显示出强健的表皮覆盖，重建了规则和角质化的表皮衬里，肉芽组织组织良好，有许多血管，尽管比未感染组略少。而在万古霉素治疗组，上皮出现，一般来说，仍然肥大，肉芽组织出现更少的组织。我们观察到两个治疗组的EGFR和VEGF表达升高，尽管dalbavancin治疗的小鼠更高。与未治疗的感染伤口相比，未感染组织和两种治疗组织的MMP-1和MMP-9均降低。这项研究表明，dalbavancin治疗的愈合速度更快，可能与更高的EGFR和VEGF水平有关。
Dalbavancin is an effective antibiotic that is widely used to treat skin infection. Our aim was to determine the effect of dalbavancin administration on wound healing compared to that of vancomycin and to elucidate if epidermal growth factor receptor (EGFR), matrix metalloproteinase 1 (MMP-1), MMP-9, and vascular endothelial growth factor (VEGF) could be involved in its therapeutic mechanism. A mouse model of methicillin-resistant Staphylococcus aureus (MRSA) skin infection was established. Mice were treated daily with vancomycin (10 mg/kg) and weekly with dalbavancin at day 1 (20 mg/kg) and day 8 (10 mg/kg). After 14 days, wounds were excised, and bacterial counts were performed. Wound healing was assessed by histological and immunohistochemical staining, followed by protein extraction and immunoblotting. Our microbiological results confirmed that both dalbavancin and vancomycin are effective in reducing the bacterial load in wounds. The dalbavancin group showed a strong effect compared with infected untreated animals and the vancomycin-treated group. The wounds treated with dalbavancin showed robust epidermal coverage with reconstitution of the regular and keratinized epidermal lining and well-organized granulation tissue with numerous blood vessels, although slightly less than that in the uninfected group. While in the vancomycin-treated group the epithelium appeared, in general, still hypertrophic, the granulation tissue appeared even less organized. We observed elevated EGFR and VEGF expression in both treated groups, although it was higher in dalbavancin-treated mice. MMP-1 and MMP-9 were decreased in uninfected tissue and in both treated tissues compared with untreated infected wounds. This study showed faster healing with dalbavancin treatment that might be associated with higher EGFR and VEGF levels.