An omics-based framework for assessing the health risk of antimicrobial resistance genes.
An omics-based framework for assessing the health risk of antimicrobial resistance genes.
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DOI：
10.1038/s41467-021-25096-3
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发表时间：
2021-08-06
影响因子：
16.6
通讯作者：
Zhang T
中科院分区：
文献类型：
--
作者：
Zhang AN;Gaston JM;Dai CL;Zhao S;Poyet M;Groussin M;Yin X;Li LG;van Loosdrecht MCM;Topp E;Gillings MR;Hanage WP;Tiedje JM;Moniz K;Alm EJ;Zhang T
抗生素耐药基因（ARG）在细菌中广泛存在。然而，并非所有的ARG都对公共卫生构成严重威胁，这突出表明了识别高风险ARG的重要性。在这里，我们开发了一个“基于组学”的框架来评估ARG风险，考虑人类相关富集，基因移动性和宿主致病性。我们的框架将人类相关的移动的ARG（占所有ARG的3.6%）归类为最高风险，我们进一步将其区分为“当前威胁”（排名I; 3%）-病原体中已经存在-和“未来威胁”（排名II; 0.6%）-来自非病原体的新耐药性。我们的框架确定了73个“当前威胁”ARG家庭。其中，35个属于世界卫生组织和其他文献提出的37个高风险ARG;其余38个在医院质粒中显著富集。通过评估自框架构建以来释放的所有病原体基因组，我们证实了最近转移到病原体中的ARG在等级II（“未来威胁”）中显著富集。最后，我们将该框架应用于来自粪便微生物群移植供体的肠道微生物群基因组。我们发现，尽管ARG广泛存在（73%的基因组），但只有8.9%的基因组含有高风险ARG。我们的框架提供了一种易于实施的方法来识别当前和未来的抗菌素耐药性威胁，具有潜在的临床应用，包括降低基于微生物组的干预措施的风险。抗生素耐药基因很常见，但并非所有基因都对人类健康具有高风险。在这里，作者开发了一个基于组学的框架，通过风险对基因进行排名，该框架包括人类相关环境中的富集水平，基因流动性和宿主致病性。
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. Antibiotic resistance genes are common but not all are of high risk to human health. Here, the authors develop an omics-based framework for ranking genes by risk that incorporates level of enrichment in human associated environments, gene mobility, and host pathogenicity.
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影响因子：
5.2
作者：
Gueimonde M;Sánchez B;G de Los Reyes-Gavilán C;Margolles A
通讯作者：
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影响因子：
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通讯作者：
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通讯作者：
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