Spatial entropy drives the maintenance and dissemination of transferable plasmids.

The dissemination of transferable plasmids, a major type of mobile genetic elements (MGEs), is one main driver of antibiotic resistance outbreaks. While the plasmid persistence condition in well-mixed environments has been extensively studied, most microbiota in nature are spatially heterogeneous. However, our knowledge regarding how spatial landscape shapes plasmid maintenance and dissemination remains limited. Here we establish a theoretical framework describing plasmid spread over a metacommunity of multiple patches. By analyzing the gene flow dynamics on randomly generated landscapes, we show that plasmid survival and dispersal are dictated by a simple feature of the landscape, spatial entropy. Reducing entropy speeds up plasmid range expansion and allows the global maintenance of many plasmids that are predicted to be lost by classic theories. The entropy's effects are experimentally validated in E. coli metacommunities transferring a conjugative plasmid. We further examine a vast collection of prokaryotic genomes and show that prokaryotes from low-entropy environments indeed carry more abundant MGEs and antibiotic resistance genes. Our work provides critical insights into the management and control of antimicrobial resistance.