An omics-based framework for assessing the health risk of antimicrobial resistance genes

微生物群 基因组 生物 抗生素耐药性 粪便细菌疗法 计算生物学 流动遗传元素 基因组 质粒 细菌基因组大小 基因 组学 遗传学 细菌 抗生素 艰难梭菌
作者
Anni Zhang,Jeffry M. Gaston,Chengzhen L. Dai,Shijie Zhao,Mathilde Poyet,Mathieu Groussin,Xiaole Yin,Li-Guan Li,Mark C.M. van Loosdrecht,Edward Topp,Michael R. Gillings,William P. Hanage,James M. Tiedje,Katya Moniz,Eric J. Alm,Tong Zhang
出处
期刊:Nature Communications [Springer Nature]
卷期号:12 (1) 被引量:468
标识
DOI:10.1038/s41467-021-25096-3
摘要

Abstract Antibiotic resistance genes (ARGs) are widespread among bacteria. However, not all ARGs pose serious threats to public health, highlighting the importance of identifying those that are high-risk. Here, we developed an ‘omics-based’ framework to evaluate ARG risk considering human-associated-enrichment, gene mobility, and host pathogenicity. Our framework classifies human-associated, mobile ARGs (3.6% of all ARGs) as the highest risk, which we further differentiate as ‘current threats’ (Rank I; 3%) - already present among pathogens - and ‘future threats’ (Rank II; 0.6%) - novel resistance emerging from non-pathogens. Our framework identified 73 ‘current threat’ ARG families. Of these, 35 were among the 37 high-risk ARGs proposed by the World Health Organization and other literature; the remaining 38 were significantly enriched in hospital plasmids. By evaluating all pathogen genomes released since framework construction, we confirmed that ARGs that recently transferred into pathogens were significantly enriched in Rank II (‘future threats’). Lastly, we applied the framework to gut microbiome genomes from fecal microbiota transplantation donors. We found that although ARGs were widespread (73% of genomes), only 8.9% of genomes contained high-risk ARGs. Our framework provides an easy-to-implement approach to identify current and future antimicrobial resistance threats, with potential clinical applications including reducing risk of microbiome-based interventions.
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