摘要

       先前已从土壤中鉴定出古老而多样的抗生素抗性基因 (ARG)1、2、3，包括与人类病原体相同的基因 4。尽管土壤和临床抗性组之间存在明显的重叠 4,5,6，但影响土壤中 ARG 组成及其在基因组和栖息地之间移动的因素在很大程度上仍然未知 3。一般宏基因组功能通常与细菌群落的基础结构相关7,8,9,10,11,12。然而，ARG 被认为具有高度移动性 4,5,13，这促使人们推测抗性组可能与系统发育特征或生态分裂 13,14 无关。为了研究这些关系，我们对来自 18 种农业和草地土壤的 18 种抗生素的抗性进行了功能宏基因组选择。我们发现的 2,895 个 ARG 大多是新的，代表了所有主要的抗性机制 15。我们证明不同的土壤类型具有不同的抗性组，并且氮肥的添加强烈影响土壤 ARG 含量。抗性组的组成还与土壤类型之间和土壤类型内的微生物系统发育和分类结构相关。与这种强相关性一致，与测序的病原体相比，与 ARGs 同线的迁移元素（负责细菌间水平基因转移的基因，如转座酶和整合酶）在土壤中很少见，这表明 ARGs 可能不像观察到的那样容易在土壤细菌之间转移人类病原体之间。总之，我们的结果表明细菌群落组成是土壤 ARG 含量的主要决定因素，挑战了先前的假设，即水平基因转移有效地将抗性组与系统发育分离13,14。

       Ancient and diverse antibiotic resistance genes (ARGs) have previously been identified from soil1,2,3, including genes identical to those in human pathogens4. Despite the apparent overlap between soil and clinical resistomes4,5,6, factors influencing ARG composition in soil and their movement between genomes and habitats remain largely unknown3. General metagenome functions often correlate with the underlying structure of bacterial communities7,8,9,10,11,12. However, ARGs are proposed to be highly mobile4,5,13, prompting speculation that resistomes may not correlate with phylogenetic signatures or ecological divisions13,14. To investigate these relationships, we performed functional metagenomic selections for resistance to 18 antibiotics from 18 agricultural and grassland soils. The 2,895 ARGs we discovered were mostly new, and represent all major resistance mechanisms15. We demonstrate that distinct soil types harbour distinct resistomes, and that the addition of nitrogen fertilizer strongly influenced soil ARG content. Resistome composition also correlated with microbial phylogenetic and taxonomic structure, both across and within soil types. Consistent with this strong correlation, mobility elements (genes responsible for horizontal gene transfer between bacteria such as transposases and integrases) syntenic with ARGs were rare in soil by comparison with sequenced pathogens, suggesting that ARGs may not transfer between soil bacteria as readily as is observed between human pathogens. Together, our results indicate that bacterial community composition is the primary determinant of soil ARG content, challenging previous hypotheses that horizontal gene transfer effectively decouples resistomes from phylogeny13,14.

https://www.nature.com/articles/nature13377