Liu Shufeng, Zhang Youwen, Cui Yao, Du Wenran, Li Yinghao, Xiong Zhaokun, Wang Jiawen, Wu Zongzhi, Yuan Jinlong, Liu Wen
State Key Laboratory of Nutrient Use and Management, College of Resources and Environmental Sciences, China Agricultural University, Beijing 100193, PR China.
State Key Laboratory of Nutrient Use and Management, College of Resources and Environmental Sciences, China Agricultural University, Beijing 100193, PR China.
Water Res. 2025 Jul 7;286:124178. doi: 10.1016/j.watres.2025.124178.
Unveiling horizontal gene transfer (HGT) of antibiotic (ARGs) and metal(loid) resistance genes (MRGs) in hospital sewage is critical for surveilling antimicrobial resistance (AMR) mobility that poses huge threats to public health. Using metagenomic shotgun sequencing, we provided an integrate insight into AMR characters and the relevant HGT in untreated sewage from one of the world's largest comprehensive hospitals from Oct 2022 to Aug 2023. We uncovered higher richness and diversity of ARGs or MRGs than mobile genetic elements (MGEs), while MGEs exhibited the highest abundance, suggesting great HGT potentials. Higher number of ARG, MRG, and MGE subtypes and abundances of putative human pathogens were found in autumn-winter than in spring-summer. ARG- and MGE-carrying prokaryotes outcompeted non-carriers in abundances, and multi-ARG and MGE carriers outcompeted single ones. Resistome supercarriers occupying 25 % of prokaryotic abundance harbored higher functional diversity and more metabolic capacity than other prokaryotes, which could be related to more predicted HGT events. Notably, 30 %, 22 %, and 40 % of prokaryote-carrying ARGs, MRGs, and MGEs were associated with HGTs. Diversity variation of plasmids as a critical contributor to HGT was positively correlated with those of prokaryotes and ARGs or MRGs. Plasmids carrying high-risk ARGs (e.g., multidrug and tetracycline types) showed higher abundances than prokaryotes and viruses. Most bacterial taxa may undergo high levels of active viral replication (phylum-specific virus/host abundance ratios >12). Hundreds of virulent viruses could lyse abundant ARG or MRG supercarriers and hosts of multidrug, multi-metals, and As resistome, whilst one temperate virus infecting multiple Azonexus supercarriers may contribute the HGT of Hg resistome. We found the dominance of stochasticity in assembling of ARGs/MGEs rather than prokaryotes or viruses, which was likely owed to functional redundancy led by HGT. Overall, this study sheds lights on a pivotal role of HGT in driving microbial community and functionality, and provides a guidance for the optimization of the treatment strategies particularly on MGEs.
揭示医院污水中抗生素抗性基因（ARGs）和金属（类金属）抗性基因（MRGs）的水平基因转移（HGT）对于监测对抗公共卫生构成巨大威胁的抗菌药物耐药性（AMR）的流动性至关重要。利用宏基因组鸟枪法测序，我们对2022年10月至2023年8月期间来自世界上最大的综合医院之一的未经处理污水中的AMR特征及相关HGT进行了综合洞察。我们发现ARGs或MRGs的丰富度和多样性高于移动遗传元件（MGEs），而MGEs的丰度最高，这表明其具有巨大的HGT潜力。秋冬季节发现的ARG、MRG和MGE亚型数量以及假定人类病原体的丰度高于春夏季节。携带ARG和MGE的原核生物在丰度上超过了非携带者，而携带多种ARG和MGE的载体超过了单一载体。占原核生物丰度25%的抗性组超级载体比其他原核生物具有更高的功能多样性和更多的代谢能力，这可能与更多预测的HGT事件有关。值得注意的是，携带ARGs、MRGs和MGEs的原核生物中分别有30%、22%和40%与HGT相关。作为HGT关键贡献者的质粒的多样性变化与原核生物以及ARGs或MRGs的多样性变化呈正相关。携带高风险ARGs（如多药和四环素类）的质粒丰度高于原核生物和病毒。大多数细菌类群可能经历高水平的活跃病毒复制（门特异性病毒/宿主丰度比>12）。数百种烈性病毒可裂解大量的ARG或MRG超级载体以及多药、多金属和砷抗性组的宿主，而一种感染多个阿佐尼克斯超级载体的温和病毒可能促成汞抗性组的HGT。我们发现ARGs/MGEs组装过程中随机性占主导地位，而非原核生物或病毒，这可能归因于HGT导致的功能冗余。总体而言，本研究揭示了HGT在驱动微生物群落和功能方面的关键作用，并为优化治疗策略尤其是针对MGEs的策略提供了指导。
