摘要

    背景
在临床环境中，抗生素耐药性（AR）的上升令人非常关注。因此，了解AR机制，进化和全球分布是患者生存的重中之重。尽管在阐明临床菌株中AR机制方面做出了所有努力，但对其在环境微生物中的流行和进化知之甚少。我们使用了来自TARA Oceans项目的293个宏基因组样本，使用机器学习工具检测和量化了环境抗生素抗性基因（ARG）。

结果
在手动管理ARG之后，介绍了它们在全球海洋中的丰度和分布。此外，还显示了质粒水平ARG转移的潜力及其与环境和地理参数的相关性。总共99,205个环境开放阅读框（ORF）被归类为560种不同的ARG，它们赋予了对26种抗生素的抗药性。我们在推定的质粒序列中发现了24,567个ORF，这表明移动遗传元件在环境ARG传播动力学中的重要性。此外，发现了具有> = 2个推定的ARG的4804个重叠群，其中包括2个具有5个不同的ARG的质粒样重叠群，突显了天然海洋环境中多抗性微生物的潜在存在。最后，我们确定了对某些最相关的临床抗生素具有抗药性的ARG，揭示了15种与动员的粘菌素抗性基因（mcr）类似的ARGs的存在，这些基因对极地生物群落具有很高的丰度。在这些中，有5个属于精神细菌，一种包括机会性人类病原体的属。

结论
这项研究揭示了全球海洋基因组中ARGs的多样性和丰富性。我们的结果可在MySQL数据库转储格式的Zenodo上获得，以及用于分析的所有代码，包括在Github上可用的Jupyter笔记本js。我们还开发了用于数据可视化的仪表板Web应用程序http://www.resistomedb.com）。

    Background
The rise of antibiotic resistance (AR) in clinical settings is of great concern. Therefore, the understanding of AR mechanisms, evolution, and global distribution is a priority for patient survival. Despite all efforts in the elucidation of AR mechanisms in clinical strains, little is known about its prevalence and evolution in environmental microorganisms. We used 293 metagenomic samples from the TARA Oceans project to detect and quantify environmental antibiotic resistance genes (ARGs) using machine learning tools.

Results
After manual curation of ARGs, their abundance and distribution in the global ocean are presented. Additionally, the potential of horizontal ARG transfer by plasmids and their correlation with environmental and geographical parameters is shown. A total of 99,205 environmental open reading frames (ORFs) were classified as 1 of 560 different ARGs conferring resistance to 26 antibiotic classes. We found 24,567 ORFs in putative plasmid sequences, suggesting the importance of mobile genetic elements in the dynamics of environmental ARG transmission. Moreover, 4,804 contigs with >=2 putative ARGs were found, including 2 plasmid-like contigs with 5 different ARGs, highlighting the potential presence of multi-resistant microorganisms in the natural ocean environment. Finally, we identified ARGs conferring resistance to some of the most relevant clinical antibiotics, revealing the presence of 15 ARGs similar to mobilized colistin resistance genes (mcr) with high abundance on polar biomes. Of these, 5 are assigned to Psychrobacter, a genus including opportunistic human pathogens.

Conclusions
This study uncovers the diversity and abundance of ARGs in the global ocean metagenome. Our results are available on Zenodo in MySQL database dump format, and all the code used for the analyses, including a Jupyter notebook js avaliable on Github. We also developed a dashboard web application (http://www.resistomedb.com) for data visualization.

    https://academic.oup.com/gigascience/article/9/5/giaa046/5835778?login=true