Metabolic interactions control the spread of plasmid-encoded functional novelty during microbial range expansion

Surface-associated microbial communities are omnipresent on Earth. As individuals grow and divide within these communities, they undergo range expansion during which different cell-types arrange themselves across space to form spatial patterns (referred to as spatial self-organization). Metabolic interactions are important determinants of the spatial self-organization process, where they direct the spatial positionings of different cell-types. We hypothesized here a previously unexplored consequence of metabolic interactions; by directing the spatial positionings of different cell-types, they also control the horizontal spread of functional novelty during range expansion. We focused on a form of functional novelty of critical importance to human health – the conjugative transfer and proliferation of plasmid-encoded antibiotic resistance. We performed range expansion experiments and spatially-explicit individual-based computational simulations with pairs of strains of the bacterium Pseudomonas stutzeri , where one strain was a plasmid donor and the other a potential recipient. We then imposed a competitive or resource cross-feeding interaction between them. We found that interactions that increase the spatial intermixing of strains also increase plasmid conjugation. We further directly linked these effects to spatial intermixing itself. We finally showed that the ability of plasmid recipients to proliferate is determined by their spatial positionings. Our results demonstrate that metabolic interactions are indeed important determinants of the horizontal spread of functional novelty during microbial range expansion, and that the spatial positionings of different cell-types need to be considered when predicting the proliferation and fate of plasmid-encoded traits. ### Competing Interest Statement The authors have declared no competing interest.