摘要：
      各种抗生素在治疗细菌感染中的广泛使用和抗生素的广泛临床应用推动了各种抗生素耐药性基因（ARGs）的不断进化，导致耐药性问题日益严重。近几十年来，抗生素耐药基因和细菌的全球传播严重威胁着公众健康，并造成巨大的经济损失。值得注意的是，抗生素的过度使用不仅导致了抗生素耐药菌的出现，而且构成性地提高了环境微生物组的选择压力，间接加速了抗生素耐药基因的发展和进化，使环境微生物组成为抗生素耐药基因库。因此，对抗生素耐药菌进行广泛监测，尽早发现新的抗生素耐药基因，具有重要的临床意义和研究价值。然而，ARGs鉴定和分析的传统方法在很大程度上取决于可培养细菌的分子特征，很难在给定的生态位中提供抗性组的全面景观。为了应对揭示不可激活细菌中ARGs的日益必要性，功能宏基因组学成为一个很有前途的工具包，它将表型分析与下一次高通量测序相结合，它不依赖于具有靶基因的特定细菌的培养，因此它被认为是揭示所有新功能基因的强大替代品。在本综述中，我们系统地总结了功能宏基因组学领域的最新进展，并确定了它们在揭示环境中未知ARG方面的最新应用。这篇综述为深入了解抗生素的耐药机制提供了坚实的理论基础。
Abstract:
The widespread use of various antibiotics in the treatment of bacterial infections and the widespread clinical use of antibiotics drives the continuous evolution of various antibiotic resistance genes（ARGs）, leading to the increasing problem of drug resistance. The global spread of antibiotic-resistant genes and bacteria severely threatens the public health and results in tremendous economic losses in recent decades. Of note, the excessive usage of antibiotics not only led to the occurrence of antibiotics-resistant bacteria, but also constitutively elevated the selection pressure of environmental microbiome, indirectly accelerated the development and evolution of antibiotics-resistant genes, making environmental microbiome as the storage reservoir of antibiotics-resistant genes. Therefore, the extensive monitoring of antibiotics-resistant bacteria and the early exploration of new antibiotics-resistant genes are of great clinical significance and research value. However, traditional methodologies for ARGs identification and profiling largely depend on the molecular characterization of cultivable bacteria, hardly providing a comprehensive landscape of the resistome in a given ecological niche. To cope with the increasing necessity to uncover the ARGs in uncultivable bacteria, the functional metagenomics emerged as a promising toolkit that combines the phenotypic profiling with next high-throughput sequencing, it does not depend on the culture of specific bacteria with target genes, and thus it is deemed as a powerful alternative to reveal all novel functional genes. In the present review, we systematically summarized the latest advances in the field of functional metagenomics and dated their recent applications in unveiling the unknown ARGs from environments. This review offers a solid theoretical foundation for in-depth understanding the resistant mechanism of antibiotics.

http://biotech.aiijournal.com/EN/abstract/abstract13581.shtml