Nakatsuji Teruaki, Chen Tiffany H, Narala Saisindhu, Chun Kimberly A, Two Aimee M, Yun Tong, Shafiq Faiza, Kotol Paul F, Bouslimani Amina, Melnik Alexey V, Latif Haythem, Kim Ji-Nu, Lockhart Alexandre, Artis Keli, David Gloria, Taylor Patricia, Streib Joanne, Dorrestein Pieter C, Grier Alex, Gill Steven R, Zengler Karsten, Hata Tissa R, Leung Donald Y M, Gallo Richard L
Department of Dermatology, University of California, San Diego, La Jolla, CA 92092, USA.
Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92092, USA.
Sci Transl Med. 2017 Feb 22;9(378). doi: 10.1126/scitranslmed.aah4680.
The microbiome can promote or disrupt human health by influencing both adaptive and innate immune functions. We tested whether bacteria that normally reside on human skin participate in host defense by killing , a pathogen commonly found in patients with atopic dermatitis (AD) and an important factor that exacerbates this disease. High-throughput screening for antimicrobial activity against was performed on isolates of coagulase-negative (CoNS) collected from the skin of healthy and AD subjects. CoNS strains with antimicrobial activity were common on the normal population but rare on AD subjects. A low frequency of strains with antimicrobial activity correlated with colonization by The antimicrobial activity was identified as previously unknown antimicrobial peptides (AMPs) produced by CoNS species including and These AMPs were strain-specific, highly potent, selectively killed , and synergized with the human AMP LL-37. Application of these CoNS strains to mice confirmed their defense function in vivo relative to application of nonactive strains. Strikingly, reintroduction of antimicrobial CoNS strains to human subjects with AD decreased colonization by These findings show how commensal skin bacteria protect against pathogens and demonstrate how dysbiosis of the skin microbiome can lead to disease.
微生物群可通过影响适应性免疫和先天性免疫功能来促进或破坏人类健康。我们测试了通常存在于人体皮肤上的细菌是否通过杀死金黄色葡萄球菌来参与宿主防御，金黄色葡萄球菌是特应性皮炎（AD）患者中常见的病原体，也是加剧该疾病的一个重要因素。对从健康人和AD患者皮肤收集的凝固酶阴性葡萄球菌（CoNS）分离株进行了针对金黄色葡萄球菌的抗菌活性高通量筛选。具有抗菌活性的CoNS菌株在正常人群中很常见，但在AD患者中很少见。具有抗菌活性的菌株频率较低与金黄色葡萄球菌的定植相关。抗菌活性被鉴定为CoNS物种产生的以前未知的抗菌肽（AMPs），包括表皮葡萄球菌和溶血葡萄球菌。这些AMPs具有菌株特异性、高效力、能选择性地杀死金黄色葡萄球菌，并与人类AMP LL-37协同作用。将这些CoNS菌株应用于小鼠证实了它们相对于无活性菌株在体内的防御功能。令人惊讶的是，将具有抗菌作用的CoNS菌株重新引入AD患者体内可减少金黄色葡萄球菌的定植。这些发现表明共生皮肤细菌如何抵御病原体，并证明皮肤微生物群的生态失调如何导致疾病。
