Johnson Timothy A, Stedtfeld Robert D, Wang Qiong, Cole James R, Hashsham Syed A, Looft Torey, Zhu Yong-Guan, Tiedje James M
Center for Microbial Ecology, Michigan State University, East Lansing, Michigan, USA Department of Plant, Soil and Microbial Sciences, Michigan State University, East Lansing, Michigan, USA Food Safety and Enteric Pathogens Research Unit, National Animal Disease Center, Agricultural Research Service, U.S. Department of Agriculture, Ames, Iowa, USA.
Center for Microbial Ecology, Michigan State University, East Lansing, Michigan, USA Department of Civil and Environmental Engineering, Michigan State University, East Lansing, Michigan, USA.
mBio. 2016 Apr 12;7(2):e02214-15. doi: 10.1128/mBio.02214-15.
Antibiotic resistance is a worldwide health risk, but the influence of animal agriculture on the genetic context and enrichment of individual antibiotic resistance alleles remains unclear. Using quantitative PCR followed by amplicon sequencing, we quantified and sequenced 44 genes related to antibiotic resistance, mobile genetic elements, and bacterial phylogeny in microbiomes from U.S. laboratory swine and from swine farms from three Chinese regions. We identified highly abundant resistance clusters: groups of resistance and mobile genetic element alleles that cooccur. For example, the abundance of genes conferring resistance to six classes of antibiotics together with class 1 integrase and the abundance of IS6100-type transposons in three Chinese regions are directly correlated. These resistance cluster genes likely colocalize in microbial genomes in the farms. Resistance cluster alleles were dramatically enriched (up to 1 to 10% as abundant as 16S rRNA) and indicate that multidrug-resistant bacteria are likely the norm rather than an exception in these communities. This enrichment largely occurred independently of phylogenetic composition; thus, resistance clusters are likely present in many bacterial taxa. Furthermore, resistance clusters contain resistance genes that confer resistance to antibiotics independently of their particular use on the farms. Selection for these clusters is likely due to the use of only a subset of the broad range of chemicals to which the clusters confer resistance. The scale of animal agriculture and its wastes, the enrichment and horizontal gene transfer potential of the clusters, and the vicinity of large human populations suggest that managing this resistance reservoir is important for minimizing human risk.
Agricultural antibiotic use results in clusters of cooccurring resistance genes that together confer resistance to multiple antibiotics. The use of a single antibiotic could select for an entire suite of resistance genes if they are genetically linked. No links to bacterial membership were observed for these clusters of resistance genes. These findings urge deeper understanding of colocalization of resistance genes and mobile genetic elements in resistance islands and their distribution throughout antibiotic-exposed microbiomes. As governments seek to combat the rise in antibiotic resistance, a balance is sought between ensuring proper animal health and welfare and preserving medically important antibiotics for therapeutic use. Metagenomic and genomic monitoring will be critical to determine if resistance genes can be reduced in animal microbiomes, or if these gene clusters will continue to be coselected by antibiotics not deemed medically important for human health but used for growth promotion or by medically important antibiotics used therapeutically.
抗生素耐药性是一项全球性的健康风险，但畜牧业对个体抗生素耐药等位基因的基因背景及富集情况的影响仍不明确。我们采用定量PCR结合扩增子测序技术，对来自美国实验猪以及中国三个地区猪场的微生物群落中与抗生素耐药性、可移动遗传元件及细菌系统发育相关的44个基因进行了定量和测序。我们鉴定出了高度丰富的耐药簇：即共同出现的耐药和可移动遗传元件等位基因组。例如，在中国三个地区，赋予对六类抗生素耐药性的基因丰度与1类整合酶以及IS6100型转座子的丰度直接相关。这些耐药簇基因可能在农场微生物基因组中共同定位。耐药簇等位基因显著富集（高达16S rRNA丰度的1%至10%），这表明多重耐药细菌在这些群落中可能是常态而非例外。这种富集在很大程度上独立于系统发育组成；因此，耐药簇可能存在于许多细菌类群中。此外，耐药簇包含的耐药基因赋予对多种抗生素的耐药性，与农场中抗生素的具体使用情况无关。对这些簇的选择可能是由于仅使用了该簇赋予耐药性的多种化学物质中的一部分。畜牧业及其废弃物的规模、这些簇的富集和水平基因转移潜力以及靠近大量人群的情况表明，管理这一耐药库对于将人类风险降至最低至关重要。
农业中使用抗生素会导致共现的耐药基因簇，这些基因簇共同赋予对多种抗生素的耐药性。如果单个抗生素与整套耐药基因存在遗传联系，那么使用单一抗生素可能会选择出整套耐药基因。未观察到这些耐药基因簇与细菌种类之间的联系。这些发现促使我们更深入地了解耐药基因和可移动遗传元件在耐药岛中的共定位情况及其在整个受抗生素影响的微生物群落中的分布。随着各国政府寻求应对抗生素耐药性的上升，需要在确保动物健康和福利与保留用于治疗的重要医用抗生素之间寻求平衡。宏基因组和基因组监测对于确定动物微生物群落中的耐药基因是否能够减少，或者这些基因簇是否会继续被对人类健康并非重要的用于促进生长的抗生素或用于治疗的重要医用抗生素共选择至关重要。
