Mobilome affect the dissemination of antibiotic resistance genes (ARGs) of clinical importance into the natural environment

The prevalence of antibiotic resistance genes (ARGs) in the environment is a quintessential One Health issue that threats both human and ecosystem health; however, the source and transmission of ARGs, especially clinically important ARGs (CLIARGs), in the environment has not yet been well studied. In the present study, shotgun metagenomic approaches were used to characterize the microbiome, resistome, and mobilome composition in human feces and six different environment sample types in South China. Overall, the resistome harbored 157 CLIARGs, with specific ARG hotspots (e.g., human feces, wastewater treatment plants, livestock manure and wastewater) excreting significantly higher abundance of CLIARGs compared with the natural environment. A redundancy analysis (RDA) analysis was performed and revealed that the bacterial community compositions and mobile genetic elements (MGEs) explained 55.08% and 34.68% of the variations in ARG abundance, respectively, indicating that both bacterial community and MGEs are key contributors to the maintenance and dissemination of CLIARGs in environment. The network analysis revealed non-random co-occurrence patterns between 200 bacterial genera and 147 CLIARGs, as well as between 135 mobile genetic elements (MGEs) and 123 CLIARGs. In addition to numerous co-shared CLIARGs among different sample types, the source tracking program based on the FEAST probabilistic model was used to estimate the relative contributions of the CLIARGs from potential sources to the natural environment. The source tracking analysis results delineated that mobilome, more than microbiome, contributed CLIARG transmission from those ARG hotspots into natural environment, and the MGEs in WWTPs seems to played the most significant role in the spread of CLIARGs to the natural environment (average contribution 32.9%–46.4%). Overall, this study demonstrated the distribution and dissemination of CLIARGs in the environment, and aimed to better inform strategies to control the spread of CLIARGs into the natural environment.