Department of Laboratory Medicine, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200127, China.
Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education, Wuhan University School of Pharmaceutical Sciences, Wuhan, 430071, China.
Microbiome. 2020 Jun 5;8(1):85. doi: 10.1186/s40168-020-00866-1.
The alarming spread of antimicrobial resistance requires the development of novel anti-infective drugs. Despite the recent research focus on the human microbiome and its likely value to understand and exploit inter-bacterial inhibitory phenomena as a source for antimicrobial strategies, the human microbiota has barely been investigated for the purpose of drug development.
We performed a large screen analyzing over 3000 human skin isolates to evaluate bacterial competition within the human skin microbiota as a basis for the development of anti-infective therapeutics. We discovered a Staphylococcus hominis strain with strong and broad activity against Gram-positive pathogens that was mediated by the bacteriocin micrococcin P1 (MP1). In "probiotic" approaches, this strain led to reduced Staphylococcus aureus infection and accelerated closure of S. aureus-infected wounds. Furthermore, we used a nanoparticle strategy to overcome the physico-chemical limitations often encountered with natural substances such as MP1 and demonstrate a significant reduction of S. aureus infection by MP1-loaded nanoparticles.
Our study gives examples of how analysis of bacterial interactions in the human microbiota can be explored for the development of novel, effective anti-infective strategies. Video Abstract.
抗菌药物耐药性的惊人传播需要开发新型抗感染药物。尽管最近的研究重点是人类微生物组及其作为抗菌策略来源理解和利用细菌间抑制现象的可能价值，但人类微生物组几乎没有被用于药物开发。
我们进行了一项大型筛选实验，分析了 3000 多个人体皮肤分离物，以评估人类皮肤微生物组内的细菌竞争，作为开发抗感染治疗方法的基础。我们发现了一种对革兰氏阳性病原体具有强大而广泛活性的表皮葡萄球菌菌株，该活性由细菌素微球菌 P1（MP1）介导。在“益生菌”方法中，该菌株可减少金黄色葡萄球菌感染并加速金黄色葡萄球菌感染伤口的愈合。此外，我们使用纳米颗粒策略克服了天然物质（如 MP1）经常遇到的物理化学限制，并证明负载 MP1 的纳米颗粒可显著减少金黄色葡萄球菌感染。
我们的研究为如何分析人类微生物组中的细菌相互作用以开发新型有效抗感染策略提供了范例。
