The interplay between ecological networks drives host-plasmid community dynamics

Ying-Jie Wang , Kaitlin Schaal, Johannes Nauta, Armun Liaghat, Manlio De Domenico, James Hall, Shai Pilosof

Plasmids drive bacterial evolution by transferring adaptive traits, such as metabolism and antimicrobial resistance, between members of microbial communities. There are trends and barriers to plasmid transmission, which likely emerge from both host-plasmid interactions (e.g. plasmid host ranges), and plasmid-plasmid interactions (e.g. plasmid incompatibility). However, while both interaction networks likely play a joint role in driving the dynamics of plasmids and species in a microbiome, they have only been studied separately. We used an agent-based model to simulate multihost-multiplasmid community dynamics, manipulating network structures. We reveal that the interplay between network structures affects host coexistence, population composition, and plasmid prevalence. Specifically, modular and hub-structured plasmid incompatibility promotes bacteria coexistence, and a modular host-plasmid infection network promotes plasmid diversity. We experimentally validated our model using a 3-bacteria-2-plasmid system with a known modular infection network, showing that a structured interaction network was necessary to recapitulate experimental results. By combining modeling and experiment we highlight the importance of network structures to plasmid maintenance dynamics. Our results indicate that integrating multiple interaction types is necessary to predict the fate of plasmids in microbial communities, and highlight a need to understand both host-plasmid and plasmid-plasmid interactions when considering the spread of high-impact plasmids in microbiomes. More broadly, our work highlights the importance of explicitly considering the interplay between ecological interactions to understand the dynamics of systems involving multiple hosts and infectious agents.