The study investigates the relationship between host-plasmid networks and antimicrobial resistance (AMR) genes in wastewater. Using a plasmid population model, the authors show that beneficial plasmids interact with more hosts than costly plasmids in a community with multiple hosts and plasmids. They then analyze a natural host-plasmid network from a wastewater sample using Hi-C metagenomics data. The results confirm that AMR encoding plasmids, which are likely to have positive fitness effects on their hosts, interact with more bacterial taxa than non-AMR plasmids and play a crucial role in connecting the entire network. This highlights the impact of antibiotics on restructuring host-plasmid networks by increasing the benefits of AMR-carrying plasmids, which can have significant consequences for the spread of AMR genes. The study also suggests that AMR-carrying plasmids are associated with a broader range of hosts, making them more resilient to bacterial strain turnover. The findings provide insights into the ecological and evolutionary dynamics of plasmid transmission and the spread of AMR in complex microbial communities.The study investigates the relationship between host-plasmid networks and antimicrobial resistance (AMR) genes in wastewater. Using a plasmid population model, the authors show that beneficial plasmids interact with more hosts than costly plasmids in a community with multiple hosts and plasmids. They then analyze a natural host-plasmid network from a wastewater sample using Hi-C metagenomics data. The results confirm that AMR encoding plasmids, which are likely to have positive fitness effects on their hosts, interact with more bacterial taxa than non-AMR plasmids and play a crucial role in connecting the entire network. This highlights the impact of antibiotics on restructuring host-plasmid networks by increasing the benefits of AMR-carrying plasmids, which can have significant consequences for the spread of AMR genes. The study also suggests that AMR-carrying plasmids are associated with a broader range of hosts, making them more resilient to bacterial strain turnover. The findings provide insights into the ecological and evolutionary dynamics of plasmid transmission and the spread of AMR in complex microbial communities.