Liao Hanpeng, Wen Chang, Huang Dan, Liu Chen, Gao Tian, Du Qiyao, Yang Qiu-E, Jin Ling, Ju Feng, Yuan Mengting Maggie, Tang Xiang, Yu Pingfeng, Zhou Shungui, Alvarez Pedro J, Friman Ville-Petri
Fujian Provincial Key Laboratory of Soil Environmental Health and Regulation, College of Resources and Environment, Fujian Agriculture and Forestry University, Fuzhou, 350002, China.
College of Environmental and Resource Sciences, Zhejiang University, Hangzhou, 310058, China.
Microbiome. 2025 May 19;13(1):127. doi: 10.1186/s40168-025-02117-7.
Antimicrobial resistance poses a substantial and growing threat to global health. While antibiotic resistance genes (ARGs) are tracked most closely in clinical settings, their spread remains poorly understood in non-clinical environments. Mitigating the spread of ARGs in non-clinical contexts such as soil could limit their enrichment in food webs.
Multi-omics (involving metagenomics, metatranscriptomics, viromics, and metabolomics) and direct experimentation show that targeting keystone bacterial taxa by phages can limit ARG maintenance and dissemination in natural soil environments. Based on the metagenomic analysis, we first show that phages from activated sludge can regulate soil microbiome composition and function in terms of reducing ARG abundances and changing the bacterial community composition. This effect was mainly driven by a reduction in the abundance and activity of Streptomyces genus, which is well known for encoding both antibiotic resistance and synthesis genes. To validate the significance of this keystone species for the loss of ARGs, we enriched phage consortia specific to Streptomyces and tested their effect on ARG abundances on 48 soil samples collected across China. We observed a consistent reduction in ARG abundances across all soils, confirming that Streptomyces-enriched phages could predictably change the soil microbiome resistome and mitigate the prevalence of ARGs. This study highlights that phages can be used as ecosystem engineers to control the spread of antibiotic resistance in the environment.
Our study demonstrates that some bacterial keystone taxa are critical for ARG maintenance and dissemination in soil microbiomes, and opens new ecological avenues for microbiome modification and resistome control. This study advances our understanding of how metagenomics-informed phage consortia can be used to predictably regulate soil microbiome composition and functioning by targeting keystone bacterial taxa. Video Abstract.
抗菌素耐药性对全球健康构成了重大且日益严重的威胁。虽然抗生素耐药基因（ARGs）在临床环境中受到最密切的追踪，但它们在非临床环境中的传播情况仍知之甚少。减轻ARGs在土壤等非临床环境中的传播可能会限制其在食物网中的富集。
多组学（包括宏基因组学、宏转录组学、病毒组学和代谢组学）和直接实验表明，噬菌体靶向关键细菌类群可以限制ARGs在天然土壤环境中的维持和传播。基于宏基因组分析，我们首先表明，来自活性污泥的噬菌体可以通过降低ARGs丰度和改变细菌群落组成来调节土壤微生物组的组成和功能。这种效应主要是由链霉菌属丰度和活性的降低驱动的，链霉菌属以编码抗生素抗性和合成基因而闻名。为了验证这种关键物种对ARGs流失的重要性，我们富集了链霉菌属特有的噬菌体群落，并测试了它们对中国各地采集的48个土壤样本中ARGs丰度的影响。我们观察到所有土壤中ARGs丰度都持续下降，证实了富含链霉菌属的噬菌体可以可预测地改变土壤微生物组抗性组并减轻ARGs的流行。这项研究强调，噬菌体可用作生态系统工程师来控制环境中抗生素抗性的传播。
我们的研究表明，一些细菌关键类群对土壤微生物组中ARGs的维持和传播至关重要，并为微生物组修饰和抗性组控制开辟了新的生态途径。这项研究推进了我们对如何利用宏基因组学指导的噬菌体群落通过靶向关键细菌类群来可预测地调节土壤微生物组组成和功能的理解。视频摘要。
