A segregated model for plasmid content and product synthesis in unstable binary fission recombinant organisms

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Abstract
Plasmid propagation in populations of unstable, binary fission recombinant organisms has been studied using a segregated, population balance mathematical model. Segregated models have the advantage of direct incorporation of basic information on mechanisms and kinetics of plasmid replication and segregation at the single‐cell level. The distribution of cellular plasmid content and specific rates of plasmid gene expression have been obtained for several single‐cell models of plasmid replication, partition, and gene expression. Plasmid replication kinetics during cell growth significantly influence the plasmid content distribution. In the case of transient growth of plasmid‐containing and plasmid‐free cells in partially selective medium, the degree of selection required for stable maintenance of plasmid‐containing cells has been determined. Guidelines are presented for applicability of simpler, nonsegregated models and for evaluation of the parameters in these models based on single‐cell mechanisms and associated parameters.