Harnessing phage consortia to mitigate the soil antibiotic resistome by targeting keystone taxa Streptomyces
Hanpeng Liao, Chang Wen, Dan Huang, Chen Liu, Tian Gao, Qian Du, Qiue Yang, Ling Jin, Feng Ju, Mengting Yuan, Xiang Tang, Pingfeng Yu, Shungui Zhou, Pedro J. J. Alvarez, Ville‐Petri Friman
Abstract
BACKGROUND: 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. RESULTS: 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. CONCLUSION: 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.