R-055. High Nutrient Levels and Spatial Structure Mediate Invasion of IncP-1 Plasmids in Bacterial Populations
In spite of the importance of self-transmissible plasmids in bacterial adaptation, illustrated by the rise of multi-drug resistant pathogens, we currently have a poor understanding of plasmid dynamics in bacterial populations. It is not known if and how plasmids persist in and spread through (invade) a population when there is no selection for plasmid-encoded traits. Moreover, the differences in plasmid dynamics between spatially structured and completely mixed populations are poorly understood. We hypothesize that self-transmissible IncP-1 plasmids can invade a population of plasmid-free hosts in the absence of selection when initially very rare, but only in spatially structured habitats and when nutrients are regularly replenished. Our goal was to test this hypothesis using a joint experimental/theoretical approach. We compared the invasiveness of plasmid pB10 in E. coli over a period of 15 days, when the initial fraction of plasmid-bearing (p+) cells was as low as 10-7, using protocols that differed in the degree of spatial structure and nutrient levels. To further explore the mechanisms underlying the plasmid population dynamics we developed a spatially explicit mathematical model, since existing models based on ordinary differential equations assume complete mixing of cells. When bacteria were grown on filters on top of agar medium, and filters were transferred to fresh medium daily, the p+ fraction increased to ca. 10% after 15 days, while almost complete invasion was observed when the population structure was disturbed daily. The plasmid was not able to invade in liquid medium. Thus spatial structure with regular cell rearrangement was most conducive to invasion. When the cells remained on the same agar plate and were not provided fresh medium, plasmid invasion was hampered, indicating that nutrient availability is essential for successful plasmid invasion. Model simulations closely matched the results and allowed estimation of the effects of alternative experimental parameters. Our results show that spatial structure and nutrient availability can be key determinants in the invasiveness of plasmids in bacterial populations.