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.

Key words: functional metagenomics, environmental microbiome, novel resistance genes, antibiotic