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

Abstract

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.

Physical contacts between sparse biofilms promote plasmid transfer and generate functional novelty

“…In addition to the absolute number of plasmid donors along the collision boundary, we hypothesized that spatial intermixing of different populations along the collision boundary is also an important determinant of plasmid spread after biofilm collision. As the distance between the initial inocula increases, we expected plasmid-carrying and plasmid-free cells to become increasingly spatially segregated due to longer expansion times (as reported in [17,18]), and lead to less efficient plasmid transfer both between biofilms and within the recipient biofilm upon collision. We tested two potential effects associated with the spatial intermixing of plasmid-carrying and plasmid-free cells that can modulate the extent of plasmid spread into an adjacent biofilm.…”

“…To better understand plasmid dynamics in biofilms, it is thus necessary to delineate plasmid transfer occurring within biofilms and at the biofilm boundaries, and to determine whether plasmid transfer in these scenarios is driven by the same or different mechanisms. In addition to space and nutrient availability, the spatial arrangement of cells across a surface is another important determinant of plasmid transfer and spread [15,17,18]. During biofilm growth and concomitant expansion across surfaces, the component microbial populations typically spatially segregate from each other as a consequence of drift at the expansion edge [19].…”

“…This expectation has been confirmed in natural systems such as the mouse gut [16], where transfer occurs only at the edges of the mucus layer covering epithelial cells. Recent studies on bacterial communities growing across nutrient-rich agar surfaces, however, show that plasmid transfer is pervasive within biofilms as long as cells are actively growing (i.e., undergoing range expansion, [17, 18]). To better understand plasmid dynamics in biofilms, it is thus necessary to delineate plasmid transfer occurring within biofilms and at the biofilm boundaries, and to determine whether plasmid transfer in these scenarios is driven by the same or different mechanisms.…”

“…In addition to space and nutrient availability, the spatial arrangement of cells across a surface is another important determinant of plasmid transfer and spread [15, 17, 18]. During biofilm growth and concomitant expansion across surfaces, the component microbial populations typically spatially segregate from each other as a consequence of drift at the expansion edge [19].…”

“…This process has important effects on biofilm diversity [20, 21], stability [22], and functioning [23]. Plasmids transfer to greater extents within communities with highly spatially intermixed populations [18]. This effect is ascribed to the higher number of cell-cell contacts between plasmid-free and plasmid-carrying cells, which increases the number of possible plasmid transfer events [11, 24, 25].…”