摘要
      由于食用复合饲料和接受药物治疗，养殖动物产生的粪便中含有过量有毒重金属，而这些重金属的存在可能会加剧在粪便处理和施用过程中通过共同选择传播耐药性基因的风险。然而，关于重金属与抗微生物耐药性之间的联系的研究仍然缺乏。在本研究中，宏基因组测序被用于探索环境毒性重金属的共同选择对粪肥抗性的影响。相关性网络分析表明，金属抗性基因（MRGs），尤其是铜（Cu）和锌（Zn），与多种类型的抗生素抗性基因（ARGs）呈正相关，并形成复杂的网络。大多数同时与MRG和ARG共存的细菌都是变形菌门的成员，占相关网络中总微生物物种的54.7%。剩下的细菌属于厚壁菌门、拟杆菌门和放线菌门。在四个门中，与其他MRG类型相比，铜和锌抗性基因与ARG的相关性更为复杂，反映了在高铜和锌水平的选择压力下ARG共选择的发生。此外，分别约64.8%、59.1%和68.4%的与质粒、病毒和原噬菌体的存在相关的MRG具有铜或锌抗性，并且它们与各种ARG共同发生，这表明可移动的遗传元件参与介导响应铜和锌压力的ARG共选择。结果表明，饲料中重金属添加剂的使用通过共同选择诱导粪肥中耐药性基因的增加，加剧了抗微生物耐药性从畜牧场扩散到粪肥地的风险。
Abstract
Farmed animals produce excrement containing excessive amounts of toxic heavy metals as a result of consuming compound feed as well as receiving medical treatments, and the presence of these heavy metals may aggravate the risk of spreading drug-resistance genes through co-selection during manure treatment and application processes. However, research on the association between heavy metals and antimicrobial resistance is still lacking. In this study, metagenomic sequencing was used to explore the effects of the co-selection of environmentally toxic heavy metals on the resistome in manure. A relevance network analysis showed that metal-resistance genes (MRGs), especially for copper (Cu) and zinc (Zn), were positively correlated with multiple types of antibiotic-resistance genes (ARGs) and formed a complex network. Most bacteria that co-occurred with both MRGs and ARGs simultaneously are members of Proteobacteria and accounted for 54.7% of the total microbial species in the relevance network. The remaining bacteria belonged to Firmicutes, Bacteroidetes and Actinobacteria. Among the four phyla, Cu- and Zn-resistance genes had more complex correlations with ARGs than other MRG types, reflecting the occurrence of ARG co-selection under the selective pressure of high Cu and Zn levels. In addition, approximately 64.8%, 59.1% and 68.4% of MRGs that correlated with the presence of plasmids, viruses and prophages, respectively, are Cu- or Zn-resistant, and they co-occurred with various ARGs, indicating that mobile genetic elements participate in mediating ARG co-selection in response to Cu and Zn pressure. The results indicated that the use of heavy-metal additives in feed induces the increases of drug resistance genes in manure through co-selection, aggravating the risk of antimicrobial resistance diffusion from animal farm to manure land applications.

https://www.sciencedirect.com/science/article/pii/S014765132200495X