摘要
      抗生素耐药性病原体构成了日益严重的公共卫生问题。因此，迫切需要更好地了解导致这一扩张的基本过程。重金属/杀生物剂和抗生素耐药性基因（ARGs）的共同选择被认为是促进抗微生物耐药性（AMR）增殖的一种潜在机制。本文旨在阐明这种相互作用，并利用抗生素使用的差异来推断养猪环境中非抗生素因素金属和杀生物剂的共同选择模式。我们检测了278只连续接触抗生素的猪的肠道宏基因组，仅在断奶时和未接触抗生素时。金属作为生长促进剂和杀生物剂作为消毒剂目前在畜牧业中几乎没有受到限制。持续接触抗生素的猪表现出ARGs和其他遗传元素的最高共现性，而有限使用抗生素的猪仍然表现出大量的共现性。属于肠杆菌科的病原体表现出增加的共现现象，这表明这种维持不是从动员库中随机选择的过程，而是属于特定的系统发育分支。这些结果表明，无论目前抗生素的使用情况如何，金属和杀生物剂都对集约农业产生的ARGs表现出强烈的选择性压力。
Abstract
Antibiotic-resistant pathogens constitute an escalating public health concern. Hence a better understanding of the underlying processes responsible for this expansion is urgently needed. Co-selection of heavy metal/biocide and antibiotic resistance genes (ARGs) has been suggested as one potential mechanism promoting the proliferation of antimicrobial resistance (AMR). This paper aims to elucidate this interplay and exploit differences in antibiotic usage to infer patterns of co-selection by the non-antibiotic factors metals and biocides in the context of pig farming. We examined 278 gut metagenomes from pigs with continuous antibiotic exposure, only at weaning and at no exposure. Metals as growth promoters and biocides as disinfectants are currently used with little restrictions in stock farming. The pigs under continuous antibiotic exposure displayed the highest co-occurrence of ARGs and other genetic elements while the pigs under limited use of antibiotics still showed abundant co-occurrences. Pathogens belonging to Enterobacteriaceae displayed increased co-occurrence phenomena, suggesting that this maintenance is not a random selection process from a mobilized pool but pertains to specific phylogenetic clades. These results suggest that metals and biocides displayed strong selective pressures on ARGs exerted by intensive farming, regardless of the current use of antibiotics.

https://www.sciencedirect.com/science/article/pii/S0160412021005249