Our skin is home to a diverse community of commensal microorganisms integral to cutaneous function. However, microbial dysbiosis and barrier perturbation increase the risk of local and systemic infection. is a particularly problematic bacterial pathogen, with high levels of antimicrobial resistance and direct association with poor healing outcome. Innovative approaches are needed to selectively kill skin pathogens, such as , without harming the resident microbiota. Here we provide important data on the selectivity and efficacy of an -targeted endolysin (XZ.700) within the complex living skin/wound microbiome. Initial cross-species comparison using Nanopore long-read sequencing identified the translational potential of porcine, rather than murine, skin for human-relevant microbiome studies. We therefore performed an interventional study in pigs to assess the impact of endolysin administration on the microbiome. XZ.700 selectively inhibited endogenous porcine , restoring microbial diversity and promoting multiple aspects of wound repair. Subsequent mechanistic studies confirmed the importance of this microbiome modulation for effective healing in human skin. Taken together, these findings strongly support further development of -targeted endolysins for future clinical management of skin and wound infections.

中文翻译：

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选择性去除金黄色葡萄球菌可恢复皮肤微生物组并加速受伤后的组织修复

我们的皮肤是皮肤功能不可或缺的多样化共生微生物群落的家园。然而，微生物失调和屏障扰动增加了局部和全身感染的风险。是一种特别成问题的细菌病原体，具有高水平的抗菌药物耐药性，并与不良的愈合结果直接相关。需要创新的方法来选择性地杀死皮肤病原体，例如，而不损害常驻微生物群。在这里，我们提供了有关复杂活体皮肤/伤口微生物群中靶向细胞内溶素 (XZ.700) 的选择性和功效的重要数据。使用 Nanopore 长读长测序进行的初步跨物种比较确定了猪（而不是鼠）皮肤用于人类相关微生物组研究的转化潜力。因此，我们对猪进行了一项介入研究，以评估内溶素给药对微生物组的影响。XZ.700选择性抑制内源性猪，恢复微生物多样性并促进伤口修复的多个方面。随后的机制研究证实了这种微生物组调节对于人类皮肤有效愈合的重要性。总而言之，这些发现有力地支持了进一步开发靶向细胞内溶素，用于未来皮肤和伤口感染的临床管理。