美国宾夕法尼亚大学Cesar de la Fuente-Nunez等研究人员合作发现，人类微生物组的挖掘揭示一个未被开发的肽类抗生素来源。相关论文于2024年8月19日在线发表于国际学术期刊《细胞》。

研究人员计算筛选了1773个人类宏基因组中报告的444054个潜在小蛋白家族，以寻找抗微生物特性，识别出323个编码在小开放阅读框（smORF）中的候选肽。为了验证计算预测，研究人员合成了78种肽，并在体外筛选其抗微生物活性，其中70.5%显示出抗微生物活性。由于这些化合物与先前报告的抗微生物肽不同，研究人员将其称为smORF编码肽（SEP）。

SEP通过靶向细菌膜、相互协同作用和调节肠道共生菌来杀死细菌，这表明它们不仅能对抗病原体，还有可能在重新配置微生物组群落中发挥作用。主要候选肽在小鼠皮肤脓肿和深部大腿感染模型中表现出抗感染活性。值得注意的是，来自Prevotella copri的prevotellin-2表现出与常用抗生素多黏菌素B相当的活性。该报告支持了在人类微生物组中存在数百种适合临床转化的抗微生物物质。

据了解，耐药菌的出现速度超过了传统抗生素的发现进展。

附：英文原文

Title: Mining human microbiomes reveals an untapped source of peptide antibiotics

Author: Marcelo D.T. Torres, Erin F. Brooks, Angela Cesaro, Hila Sberro, Matthew O. Gill, Cosmos Nicolaou, Ami S. Bhatt, Cesar de la Fuente-Nunez

Issue&Volume: 2024-08-19

Abstract: Drug-resistant bacteria are outpacing traditional antibiotic discovery efforts. Here, we computationally screened 444,054 previously reported putative small protein families from 1,773 human metagenomes for antimicrobial properties, identifying 323 candidates encoded in small open reading frames (smORFs). To test our computational predictions, 78 peptides were synthesized and screened for antimicrobial activity in vitro, with 70.5% displaying antimicrobial activity. As these compounds were different compared with previously reported antimicrobial peptides, we termed them smORF-encoded peptides (SEPs). SEPs killed bacteria by targeting their membrane, synergizing with each other, and modulating gut commensals, indicating a potential role in reconfiguring microbiome communities in addition to counteracting pathogens. The lead candidates were anti-infective in both murine skin abscess and deep thigh infection models. Notably, prevotellin-2 from Prevotella copri presented activity comparable to the commonly used antibiotic polymyxin B. Our report supports the existence of hundreds of antimicrobials in the human microbiome amenable to clinical translation.

DOI: 10.1016/j.cell.2024.07.027

Source: https://www.cell.com/cell/fulltext/S0092-8674(24)00802-X