Lugdunin amplifies innate immune responses in the skin in synergy with host- and microbiota-derived factors
Lugdunin amplifies innate immune responses in the skin in synergy with host- and microbiota-derived factors
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DOI：
10.1038/s41467-019-10646-7
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发表时间：
2019-06-21
影响因子：
16.6
通讯作者：
Schittek, Birgit
中科院分区：
文献类型：
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作者：
Bitschar, Katharina;Sauer, Birgit;Schittek, Birgit
最近，我们的研究小组发现了一种新的环肽抗生素lugdunin，它可以抑制人类和啮齿动物的金黄色葡萄球菌上皮定植。在这项工作中，我们分析了其作为单一药物或与其他微生物群或宿主衍生因子联合使用时的免疫调节和抗菌潜力。我们发现，用lugdunin联合微生物源性因子预处理原代人角质形成细胞或小鼠皮肤可显著减少金黄色葡萄球菌的定植。此外，lugdunin增加人角质形成细胞和小鼠皮肤中LL-37和CXCL8/MIP-2的表达和释放，并通过TLR/MyD88依赖机制导致体内单核细胞和中性粒细胞的募集。有趣的是，lugdunin通过与LL-37和皮杀素衍生肽的协同抗菌活性来消除金黄色葡萄球菌。总之，我们的研究结果表明，lugdunin提供了针对金黄色葡萄球菌的多层次保护，因此可能成为未来金黄色葡萄球菌皮肤感染的有希望的治疗选择。
Recently our groups discovered lugdunin, a new cyclic peptide antibiotic that inhibits Staphylococcus aureus epithelial colonization in humans and rodents. In this work, we analyzed its immuno-modulatory and antimicrobial potential as a single agent or in combination with other microbiota- or host-derived factors. We show that pretreatment of primary human keratinocytes or mouse skin with lugdunin in combination with microbiota-derived factors results in a significant reduction of S. aureus colonization. Moreover, lugdunin increases expression and release of LL-37 and CXCL8/MIP-2 in human keratinocytes and mouse skin, and results in the recruitment of monocytes and neutrophils in vivo, both by a TLR/MyD88 dependent mechanism. Interestingly, S. aureus elimination by lugdunin is additionally achieved by synergistic antimicrobial activity with LL-37 and dermcidin-derived peptides. In summary, our results indicate that lugdunin provides multi-level protection against S. aureus and may thus become a promising treatment option for S. aureus skin infections in the future.