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Johnson, D. R.

Publications and source records attributed to Johnson, D. R..

4 recordsLinked to original sources

Timing of antibiotic administration determines the spread of plasmid-encoded antibiotic resistance during microbial range expansion

The spread of antibiotic resistance (AR) is a major threat to global health. Plasmid-mediated horizontal gene transfer is the main mechanism by which AR is transferred between cells lying within close spatial proximity to each other. In this study, we address a fundamental question regarding the spread of AR-encoding plasmids: Is there an optimal time to administer antibiotics to minimize plasmid spread within microbial communities? We addressed this question using microbial consortia consisting of two Pseudomonas stutzeri strains, where one is an AR-encoding plasmid donor and the other a potential recipient. We allowed the strains to co-expand across a nutrient-amended surface and administered antibiotics at different points in time. We found that the extents of plasmid transfer and transconjugant proliferation have unimodal relationships with the timing of antibiotic administration, where they reach maxima at intermediate administration times. Using an individual-based model, we found that these unimodal relationships result from an interplay between the probability to acquire plasmids from neighboring cells and the probability of plasmid loss upon cell division. Our study provides novel mechanistic insights into the transfer and proliferation of AR-encoding plasmids within microbial communities and identifies the timing of antibiotic administration as an important determinant of AR spread.

microbiology↗

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

The horizontal transfer of plasmids is an important driver of microbial evolution, such as conferring antibiotic resistance (AR) to new genotypes. In biofilms, the abundance of cell-cell contacts promotes the frequent transfer of plasmids and their associated genes. In this study, we expand our knowledge about AR-encoding plasmids by investigating their transfer between discrete biofilms as the biofilms grow and physically collide with each other. Using an experimental system consisting of two fluorescently labelled Pseudomonas stutzeri strains and an Escherichia coli strain, we show that biofilm collisions promote plasmid transfer along the collision boundaries. The extent of plasmid transfer depends on the plasmid loss probability, the plasmid transfer probability, and the relative growth rates of plasmid-free and plasmid-carrying cells. We further show that the proliferation of plasmids after biofilm collision depends on the spatial positionings of plasmid-carrying cells along the collision boundary, thus establishing a link between the large-scale spatial distribution of discrete biofilms and the small-scale spatial arrangement of cells within individual biofilms. Our study reveals that plasmid transfer during biofilm collisions is determined by spatial factors operating at different organizational levels and length scales, expanding our understanding of the fate of plasmid-encoded traits in microbial communities.

microbiology↗

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.

ecology↗

Close-Range Interactions Favor Growth in Random-Paired Extracted Soil Bacteria

Species interactions at the cellular level are thought to govern the formation and functioning of microbial communities, but direct measurements of species interactions are difficult to perform between the hundreds of different species that constitute most microbial ecosystems. We developed a methodology to examine interactive growth of random cell pairs encapsulated inside 40-70 {micro}m diameter agarose beads. We focused on a sandy soil as a test microbial ecosystem. By using gentle washing procedures, we detached microbial cells from sand and encapsulated them either in the absence or presence of pure culture inoculants. We then tested whether inoculants had on average positive or negative effects on the growth of resident community members depending on the growth substrate. Surprisingly, all the tested inoculants (including Pseudomonas veronii 1YdBTEX2, Pseudomonas putida F1, Pseudomonas protegens CHA0 and Escherichia coli MG1655) stimulated the growth of 40-80 percent of sand-derived cells when grown pair-wise in close proximity (i.e., within the same bead). This was true essentially irrespective of the growth substrate. Beneficial inoculant-sand cell partnerships resulted in up to 100-fold increase in productivity of the sand cell partner and up to 100-fold decrease in that of the inoculant. However, the maximum productivity attained by inoculant-sand cell partners within beads did not surpass that of inoculants alone. Further surprisingly, random pairs of sand cells encapsulated within the same bead also benefited growth in comparison to individual sand cells in a mutualistic manner (i.e., productivity when grown together was greater than the sum of individual productivities), but less than productivities observed in partnerships with the tested inoculants. This suggests that partnerships between inoculants and sand cells are not so much characterized by competition for substrate as by carbon loss through metabolite provision of the inoculant to sand cells (competitive exploitation).

microbiology↗