集约化养殖猪抗生素耐药对人肠道耐药组的影响机理研究

Antibiotic resistance among bacteria is rapidly emerging as a global problem triggered by both misuse and excessive use of antibiotics. Although traditionally associated with clinical environments, there is substantial evidence that the propagation of antibiotic resistance among microbes is also affiliated with environmental hotspots. Excessive use of antibiotics in intensive feeding gives rise to accumulation of high level of antibiotic resistance genes (ARGs) in livestock intestinal tract, while a considerable number of ARGs were also found in human feces. The risk associated with antibiotic resistance disseminating from animal to human is an urgent public issue. However, key information such as ARG hosts, ARG co-occurrence with mobile genetic elements (MGEs) remains unknown. The goal of this proposal is to investigate and provide direct information about ARG hosts and ARG co-occurrence MGEs. Primarily, culture-free functional metagenomics and Pacific Biosciences SMRT sequencing will be performed to identify ARG-carrying contigs (ACCs) in both pig and human feces. Next, the targeted ARG host bacteria will be isolated to determine the evolutionary origins of the antibiotic-resistant bacteria (ARB) lineages in both livestock and human populations. Finally, the risk rates of ARG acquisition by enteropathogen will be evaluated. Our study will significantly facilitate the understanding of antibiotic resistance dissemination from livestock to human, and provide a clear target for the prevention and control of the spread of global resistance.

抗生素耐药已成为全球性的重大问题，耐药基因的来源也成为研究的热点。集约化养殖环境抗生素使用量巨大，养殖动物肠道中积累了高丰度的耐药基因，其中多种耐药基因广泛存在于人的肠道细菌中。虽然养殖环境已经被认为是耐药基因的储存库，但是是哪些细菌在传递给人的过程中起到了关键的作用并不明晰，可传播给病原菌耐药基因的可移动元件也未得到评估，无法指定根据特定靶标指定具体的管控策略。本项目针对这一问题，首先通过Pacbio测序耐药组文库得到携带耐药基因的共同可移动元件及宿主细菌信息，再通过分离这些目标细菌进行基因组测序，研究抗生素耐药的传播流向。解析加速耐药基因传播的可移动元件，评估其携带耐药基因传递至肠道病原菌的风险。本项目的完成为全局防控耐药的传播提供明确的靶标，促进我国制定明确的策略防控养殖环境的抗生素耐药传播。

抗生素耐药已成为全球性的重大问题，耐药基因的来源也成为研究的热点。集约化养殖环境抗生素使用量巨大，养殖动物肠道中积累了高丰度的耐药基因，其中多种耐药基因广泛存在于人的肠道细菌中。虽然养殖环境已经被认为是耐药基因的储存库，但是养殖环境细菌在传递给人的过程中起到的关键作用并不明晰，可传播给病原菌耐药基因的可移动元件也未得到评估，无法根据特定靶标指定具体的管控策略。本项目针对这一问题，对集约化养殖猪粪便和人粪便的耐药组进行共性研究，建立了养殖家猪与人肠道耐药细菌数据库，从导致耐药基因传播的关键细菌--大肠杆菌出发，研究耐药基因的传播方向；解析了加速耐药基因传播的可移动元件，评估了其携带耐药基因传递至肠道病原菌的风险。通过研究耐药基因在集约化养殖动物和人之间的传递关系，揭示了多耐药性形成以及广泛传播的原因。本项目的完成为全局防控耐药的传播提供明确的靶标，促进我国制定明确的策略防控养殖环境的抗生素耐药传播。